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82-537: In E. coli , Hfq mutants show multiple stress response related phenotypes. The Hfq protein is now known to regulate the translation of two major stress transcription factors ( σS (RpoS) and σE (RpoE) ) in Enterobacteria . It also regulates sRNA in Vibrio cholerae , a specific example being MicX sRNA . In Salmonella typhimurium , Hfq has been shown to be an essential virulence factor as its deletion attenuates

164-489: A Nobel Prize -winning biologist, devised a system called the Baltimore Classification System to classify different viruses based on their unique replication strategy. There are seven different replication strategies based on this system (Baltimore Class I, II, III, IV, V, VI, VII). The seven classes of viruses are listed here briefly and in generalities. This type of virus usually must enter

246-431: A complementary language. During transcription, a DNA sequence is read by an RNA polymerase , which produces a complementary, antiparallel RNA strand called a primary transcript . In virology , the term transcription is used when referring to mRNA synthesis from a viral RNA molecule. The genome of many RNA viruses is composed of negative-sense RNA which acts as a template for positive sense viral messenger RNA -

328-477: A CpG island while only about 6% of enhancer sequences have a CpG island. CpG islands constitute regulatory sequences, since if CpG islands are methylated in the promoter of a gene this can reduce or silence gene transcription. DNA methylation regulates gene transcription through interaction with methyl binding domain (MBD) proteins, such as MeCP2, MBD1 and MBD2. These MBD proteins bind most strongly to highly methylated CpG islands . These MBD proteins have both

410-434: A host cell and initiates replication by hijacking the host's cellular machinery to make new copies of the virus. In the lysogenic life cycle, the viral genome is incorporated into the host genome. The host genome will undergo its normal life cycle, replicating and dividing replicating the viral genome along with its own. The viral genome can be triggered to begin viral production via chemical and environmental stimulants. Once

492-414: A human cell ) generally bind to specific motifs on an enhancer and a small combination of these enhancer-bound transcription factors, when brought close to a promoter by a DNA loop, govern level of transcription of the target gene. Mediator (a complex usually consisting of about 26 proteins in an interacting structure) communicates regulatory signals from enhancer DNA-bound transcription factors directly to

574-772: A low salt condition ( 1U1S ​) and a high salt condition ( 1U1T ​), Hfq from S. aureus with bound RNA ( 1KQ2 ​) and without ( 1KQ1 ​), and the Hfq(-like) protein from M. jannaschii ( 2QTX ​). All six structures confirm the hexameric ring-shape of a Hfq protein complex. Transcription (genetics) Transcription is the process of copying a segment of DNA into RNA. Some segments of DNA are transcribed into RNA molecules that can encode proteins , called messenger RNA (mRNA). Other segments of DNA are transcribed into RNA molecules called non-coding RNAs (ncRNAs). Both DNA and RNA are nucleic acids , which use base pairs of nucleotides as

656-408: A lysogenic virus enters the lytic life cycle, it will continue in the viral production pathways and proceed with transcription / mRNA production. (ex: Cold sores, herpes simplex virus (HSV)-1, lysogenic bacteriophages, etc.) Assembly is when the newly manufactured viral proteins and genomes are gathered and put together to form immature viruses. Like the other steps, how a particular virus is assembled

738-473: A methyl-CpG-binding domain as well as a transcription repression domain. They bind to methylated DNA and guide or direct protein complexes with chromatin remodeling and/or histone modifying activity to methylated CpG islands. MBD proteins generally repress local chromatin such as by catalyzing the introduction of repressive histone marks, or creating an overall repressive chromatin environment through nucleosome remodeling and chromatin reorganization. As noted in

820-429: A molecule (in this case a virus) binds to receptor on the membrane of the cell. A series of chemical signals from this binding causes the cell to wrap the attached virus in the plasma membrane around it forming a virus-containing vesicle inside the cell. Viruses enter host cells using a variety of mechanisms, including the endocytic and non-endocytic routes. They can also fuse at the plasma membrane and can spread within

902-418: A necessary step in the synthesis of viral proteins needed for viral replication . This process is catalyzed by a viral RNA dependent RNA polymerase . A DNA transcription unit encoding for a protein may contain both a coding sequence , which will be translated into the protein, and regulatory sequences , which direct and regulate the synthesis of that protein. The regulatory sequence before ( upstream from)

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984-542: A promoter. (RNA polymerase is called a holoenzyme when sigma subunit is attached to the core enzyme which is consist of 2 α subunits, 1 β subunit, 1 β' subunit only). Unlike eukaryotes, the initiating nucleotide of nascent bacterial mRNA is not capped with a modified guanine nucleotide. The initiating nucleotide of bacterial transcripts bears a 5′ triphosphate (5′-PPP), which can be used for genome-wide mapping of transcription initiation sites. In archaea and eukaryotes , RNA polymerase contains subunits homologous to each of

1066-404: A repressor of mRNA translation . Genomic SELEX has been used to show that Hfq binding RNAs are enriched in the sequence motif 5'-AAYAAYAA-3'. Hfq was also found to act on ribosome biogenesis in E. coli , specifically on the 30S subunit. Hfq mutants accumulate higher levels of immature small subunits and decreased translation accuracy. This function on the bacterial ribosome could also account for

1148-625: A single copy of a gene. The characteristic elongation rates in prokaryotes and eukaryotes are about 10–100 nts/sec. In eukaryotes, however, nucleosomes act as major barriers to transcribing polymerases during transcription elongation. In these organisms, the pausing induced by nucleosomes can be regulated by transcription elongation factors such as TFIIS. Elongation also involves a proofreading mechanism that can replace incorrectly incorporated bases. In eukaryotes, this may correspond with short pauses during transcription that allow appropriate RNA editing factors to bind. These pauses may be intrinsic to

1230-464: A study of brain cortical neurons, 24,937 loops were found, bringing enhancers to their target promoters. Multiple enhancers, each often at tens or hundred of thousands of nucleotides distant from their target genes, loop to their target gene promoters and can coordinate with each other to control transcription of their common target gene. The schematic illustration in this section shows an enhancer looping around to come into close physical proximity with

1312-450: A variety of ways: Some viruses (such as HIV , the cause of AIDS ), have the ability to transcribe RNA into DNA. HIV has an RNA genome that is reverse transcribed into DNA. The resulting DNA can be merged with the DNA genome of the host cell. The main enzyme responsible for synthesis of DNA from an RNA template is called reverse transcriptase . In the case of HIV, reverse transcriptase

1394-415: Is rifampicin , which inhibits bacterial transcription of DNA into mRNA by inhibiting DNA-dependent RNA polymerase by binding its beta-subunit, while 8-hydroxyquinoline is an antifungal transcription inhibitor. The effects of histone methylation may also work to inhibit the action of transcription. Potent, bioactive natural products like triptolide that inhibit mammalian transcription via inhibition of

1476-409: Is a particular transcription factor that is important for regulation of methylation of CpG islands. An EGR1 transcription factor binding site is frequently located in enhancer or promoter sequences. There are about 12,000 binding sites for EGR1 in the mammalian genome and about half of EGR1 binding sites are located in promoters and half in enhancers. The binding of EGR1 to its target DNA binding site

1558-498: Is also altered in response to signals. The three mammalian DNA methyltransferasess (DNMT1, DNMT3A, and DNMT3B) catalyze the addition of methyl groups to cytosines in DNA. While DNMT1 is a maintenance methyltransferase, DNMT3A and DNMT3B can carry out new methylations. There are also two splice protein isoforms produced from the DNMT3A gene: DNA methyltransferase proteins DNMT3A1 and DNMT3A2. The splice isoform DNMT3A2 behaves like

1640-654: Is also one of the most-studied types of viruses, alongside the double-stranded DNA viruses. The positive-sense RNA viruses and indeed all genes defined as positive-sense can be directly accessed by host ribosomes to immediately form proteins. These can be divided into two groups, both of which replicate in the cytoplasm: Examples of this class include the families Coronaviridae , Flaviviridae , and Picornaviridae . The negative-sense RNA viruses and indeed all genes defined as negative-sense cannot be directly accessed by host ribosomes to immediately form proteins. Instead, they must be transcribed by viral polymerases into

1722-530: Is dependent on what type of virus it is. Assembly can occur in the plasma membrane, cytosol, nucleus, golgi apparatus, and other locations within the host cell. Some viruses only insert their genome into a capsid once the capsid is completed, while in other viruses the will capsid will wrap around the genome as it is being copied. This is the final step before a competent virus is formed. This typically involves capsid modifications that are provided enzymes (host or virus-encoded). The final step in viral replication

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1804-654: Is followed by 3' guanine or CpG sites ). 5-methylcytosine (5-mC) is a methylated form of the DNA base cytosine (see Figure). 5-mC is an epigenetic marker found predominantly within CpG sites. About 28 million CpG dinucleotides occur in the human genome. In most tissues of mammals, on average, 70% to 80% of CpG cytosines are methylated (forming 5-methylCpG or 5-mCpG). However, unmethylated cytosines within 5'cytosine-guanine 3' sequences often occur in groups, called CpG islands , at active promoters. About 60% of promoter sequences have

1886-479: Is insensitive to cytosine methylation in the DNA. While only small amounts of EGR1 transcription factor protein are detectable in cells that are un-stimulated, translation of the EGR1 gene into protein at one hour after stimulation is drastically elevated. Production of EGR1 transcription factor proteins, in various types of cells, can be stimulated by growth factors, neurotransmitters, hormones, stress and injury. In

1968-428: Is normally used to facilitate adhesion between other host cells. Entry, or penetration, is the second step in viral replication. This step is characterized by the virus passing through the plasma membrane of the host cell. The most common way a virus gains entry to the host cell is by receptor-mediated endocytosis , which comes at no energy cost to the virus, only the host cell. Receptor-mediated endocytosis occurs when

2050-599: Is not yet known. One strand of the DNA, the template strand (or noncoding strand), is used as a template for RNA synthesis. As transcription proceeds, RNA polymerase traverses the template strand and uses base pairing complementarity with the DNA template to create an RNA copy (which elongates during the traversal). Although RNA polymerase traverses the template strand from 3' → 5', the coding (non-template) strand and newly formed RNA can also be used as reference points, so transcription can be described as occurring 5' → 3'. This produces an RNA molecule from 5' → 3', an exact copy of

2132-410: Is regulated by many cis-regulatory elements , including core promoter and promoter-proximal elements that are located near the transcription start sites of genes. Core promoters combined with general transcription factors are sufficient to direct transcription initiation, but generally have low basal activity. Other important cis-regulatory modules are localized in DNA regions that are distant from

2214-413: Is release, which is when the newly assembled and mature viruses leave the host cell. How a virus releases from the host cell is dependent on the type of virus it is. One common type of release is budding. This occurs when viruses that form their envelope from the host's plasma membrane bend the membrane around the capsid. As the virus bends the plasma membrane it begins to wrap around the whole capsid until

2296-513: Is responsible for synthesizing a complementary DNA strand (cDNA) to the viral RNA genome. The enzyme ribonuclease H then digests the RNA strand, and reverse transcriptase synthesises a complementary strand of DNA to form a double helix DNA structure (cDNA). The cDNA is integrated into the host cell's genome by the enzyme integrase , which causes the host cell to generate viral proteins that reassemble into new viral particles. In HIV, subsequent to this,

2378-428: Is synthesized, at which point promoter escape occurs and a transcription elongation complex is formed. Mechanistically, promoter escape occurs through DNA scrunching , providing the energy needed to break interactions between RNA polymerase holoenzyme and the promoter. In bacteria, it was historically thought that the sigma factor is definitely released after promoter clearance occurs. This theory had been known as

2460-435: Is then transferred into the cytoplasm. Cell-to-cell fusion: Some viruses prompt specific protein expression on the surfaces of infected cells to attract uninfected cells. This interaction causes the uninfected cell to fuse with the infected cell at lower pH levels to form a multinuclear cell known as a syncytium. Endocytic routes: the process by which an intracellular vesicle is formed by membrane invagination, which results in

2542-691: The Circoviridae and Parvoviridae . They replicate within the nucleus, and form a double-stranded DNA intermediate during replication. A human Anellovirus called TTV is included within this classification and is found in almost all humans, infecting them asymptomatically in nearly every major organ . RNA viruses: The polymerase of RNA viruses lacks the proofreading functions found in the polymerase of DNA viruses. This contributed to RNA viruses having lower replicative fidelity compared to DNA viruses, causing RNA viruses to be highly mutagenic, which can increase their overall survival rate. RNA viruses lack

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2624-464: The Mfd ATPase can remove a RNA polymerase stalled at a lesion by prying open its clamp. It also recruits nucleotide excision repair machinery to repair the lesion. Mfd is proposed to also resolve conflicts between DNA replication and transcription. In eukayrotes, ATPase TTF2 helps to suppress the action of RNAP I and II during mitosis , preventing errors in chromosomal segregation. In archaea,

2706-511: The Reoviridae and Birnaviridae . Replication is monocistronic and includes individual, segmented genomes, meaning that each of the genes codes for only one protein, unlike other viruses, which exhibit more complex translation. These viruses consist of two types, however both share the fact that replication is primarily in the cytoplasm, and that replication is not as dependent on the cell cycle as that of DNA viruses. This class of viruses

2788-498: The obligate release model. However, later data showed that upon and following promoter clearance, the sigma factor is released according to a stochastic model known as the stochastic release model . In eukaryotes, at an RNA polymerase II-dependent promoter, upon promoter clearance, TFIIH phosphorylates serine 5 on the carboxy terminal domain of RNA polymerase II, leading to the recruitment of capping enzyme (CE). The exact mechanism of how CE induces promoter clearance in eukaryotes

2870-449: The "readable" complementary positive-sense. These can also be divided into two groups: Examples in this class include the families Orthomyxoviridae , Paramyxoviridae , Bunyaviridae , Filoviridae , and Rhabdoviridae (which includes rabies ). A well-studied family of this class of viruses include the retroviruses . One defining feature is the use of reverse transcriptase to convert the positive-sense RNA into DNA. Instead of using

2952-478: The 3' end of the growing mRNA chain. This use of only the 3' → 5' DNA strand eliminates the need for the Okazaki fragments that are seen in DNA replication. This also removes the need for an RNA primer to initiate RNA synthesis, as is the case in DNA replication. The non -template (sense) strand of DNA is called the coding strand , because its sequence is the same as the newly created RNA transcript (except for

3034-605: The BRCA1 promoter (see Low expression of BRCA1 in breast and ovarian cancers ). Active transcription units are clustered in the nucleus, in discrete sites called transcription factories or euchromatin . Such sites can be visualized by allowing engaged polymerases to extend their transcripts in tagged precursors (Br-UTP or Br-U) and immuno-labeling the tagged nascent RNA. Transcription factories can also be localized using fluorescence in situ hybridization or marked by antibodies directed against polymerases. There are ~10,000 factories in

3116-530: The Eta ATPase is proposed to play a similar role. Genome damage occurs with a high frequency, estimated to range between tens and hundreds of thousands of DNA damages arising in each cell every day. The process of transcription is a major source of DNA damage, due to the formation of single-strand DNA intermediates that are vulnerable to damage. The regulation of transcription by processes using base excision repair and/or topoisomerases to cut and remodel

3198-463: The RNA for templates of proteins, they use DNA to create the templates, which is spliced into the host genome using integrase . Replication can then commence with the help of the host cell's polymerases. This small group of viruses, exemplified by the Hepatitis B virus, have a double-stranded, gapped genome that is subsequently filled in to form a covalently closed circle ( cccDNA ) that serves as

3280-506: The RNA polymerase II (pol II) enzyme bound to the promoter. Enhancers, when active, are generally transcribed from both strands of DNA with RNA polymerases acting in two different directions, producing two enhancer RNAs (eRNAs) as illustrated in the Figure. An inactive enhancer may be bound by an inactive transcription factor. Phosphorylation of the transcription factor may activate it and that activated transcription factor may then activate

3362-400: The RNA polymerase and one or more general transcription factors binding to a DNA promoter sequence to form an RNA polymerase-promoter closed complex. In the closed complex, the promoter DNA is still fully double-stranded. RNA polymerase, assisted by one or more general transcription factors, then unwinds approximately 14 base pairs of DNA to form an RNA polymerase-promoter open complex. In

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3444-654: The RNA polymerase or due to chromatin structure. Double-strand breaks in actively transcribed regions of DNA are repaired by homologous recombination during the S and G2 phases of the cell cycle . Since transcription enhances the accessibility of DNA to exogenous chemicals and internal metabolites that can cause recombinogenic lesions, homologous recombination of a particular DNA sequence may be strongly stimulated by transcription. Bacteria use two different strategies for transcription termination – Rho-independent termination and Rho-dependent termination. In Rho-independent transcription termination , RNA transcription stops when

3526-1105: The XPB subunit of the general transcription factor TFIIH has been recently reported as a glucose conjugate for targeting hypoxic cancer cells with increased glucose transporter production. In vertebrates, the majority of gene promoters contain a CpG island with numerous CpG sites . When many of a gene's promoter CpG sites are methylated the gene becomes inhibited (silenced). Colorectal cancers typically have 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. However, transcriptional inhibition (silencing) may be of more importance than mutation in causing progression to cancer. For example, in colorectal cancers about 600 to 800 genes are transcriptionally inhibited by CpG island methylation (see regulation of transcription in cancer ). Transcriptional repression in cancer can also occur by other epigenetic mechanisms, such as altered production of microRNAs . In breast cancer, transcriptional repression of BRCA1 may occur more frequently by over-produced microRNA-182 than by hypermethylation of

3608-469: The ability of S.typhimurium to invade epithelial cells , secrete virulence factors or survive in cultured macrophages . In Salmonella , Hfq deletion mutants are also non motile and exhibit chronic activation of the sigma mediated envelope stress response. A CLIP-Seq study of Hfq in Salmonella has revealed 640 binding sites across the Salmonella transcriptome. The majority of these binding sites

3690-746: The brain, when neurons are activated, EGR1 proteins are up-regulated and they bind to (recruit) the pre-existing TET1 enzymes that are produced in high amounts in neurons. TET enzymes can catalyse demethylation of 5-methylcytosine. When EGR1 transcription factors bring TET1 enzymes to EGR1 binding sites in promoters, the TET enzymes can demethylate the methylated CpG islands at those promoters. Upon demethylation, these promoters can then initiate transcription of their target genes. Hundreds of genes in neurons are differentially expressed after neuron activation through EGR1 recruitment of TET1 to methylated regulatory sequences in their promoters. The methylation of promoters

3772-423: The capacity to identify and repair mismatched or damaged nucleotides, and thus, RNA genomes are prone to mutations introduced by mechanisms intrinsic and extrinsic to viral replication. RNA viruses present a therapeutic double-edged sword: RNA viruses can withstand the challenge of antiviral drugs, cause epidemics, and infect multiple host species due to their mutagenic nature, making them difficult to treat. However,

3854-676: The cell to forcefully undergo cell division , which may lead to transformation of the cell and, ultimately, cancer . An example of a family within this classification is the Adenoviridae . There is only one well-studied example in which a class 1 family of viruses does not replicate within the nucleus. This is the Poxvirus family, which comprises highly pathogenic viruses that infect vertebrates . Viruses that fall under this category include ones that are not as well-studied, but still do pertain highly to vertebrates. Two examples include

3936-407: The coding sequence is called the five prime untranslated regions (5'UTR); the sequence after ( downstream from) the coding sequence is called the three prime untranslated regions (3'UTR). As opposed to DNA replication , transcription results in an RNA complement that includes the nucleotide uracil (U) in all instances where thymine (T) would have occurred in a DNA complement. Only one of

4018-427: The coding strand (except that thymines are replaced with uracils , and the nucleotides are composed of a ribose (5-carbon) sugar whereas DNA has deoxyribose (one fewer oxygen atom) in its sugar-phosphate backbone). mRNA transcription can involve multiple RNA polymerases on a single DNA template and multiple rounds of transcription (amplification of particular mRNA), so many mRNA molecules can be rapidly produced from

4100-437: The engulfment of extracellular and membrane-bound components, in this context, a virus. Non-endocytic routes: the process by which viral particles are released into the cell by fusion of the extracellular viral envelope and the membrane of the host cell. Uncoating is the third step in viral replication. Uncoating is defined by the removal of the virion's protein "coat" and the release of its genetic material. This step occurs in

4182-417: The enhancer to which it is bound (see small red star representing phosphorylation of transcription factor bound to enhancer in the illustration). An activated enhancer begins transcription of its RNA before activating transcription of messenger RNA from its target gene. Transcription regulation at about 60% of promoters is also controlled by methylation of cytosines within CpG dinucleotides (where 5' cytosine

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4264-457: The factor. A molecule that allows the genetic material to be realized as a protein was first hypothesized by François Jacob and Jacques Monod . Severo Ochoa won a Nobel Prize in Physiology or Medicine in 1959 for developing a process for synthesizing RNA in vitro with polynucleotide phosphorylase , which was useful for cracking the genetic code . RNA synthesis by RNA polymerase

4346-583: The five RNA polymerase subunits in bacteria and also contains additional subunits. In archaea and eukaryotes, the functions of the bacterial general transcription factor sigma are performed by multiple general transcription factors that work together. In archaea, there are three general transcription factors: TBP , TFB , and TFE . In eukaryotes, in RNA polymerase II -dependent transcription, there are six general transcription factors: TFIIA , TFIIB (an ortholog of archaeal TFB), TFIID (a multisubunit factor in which

4428-421: The generation of abundant copies of its genome and packaging these copies, the virus continues infecting new hosts. Replication between viruses is greatly varied and depends on the type of genes involved in them. Most DNA viruses assemble in the nucleus while most RNA viruses develop solely in cytoplasm. Viruses multiply only in living cells. The host cell must provide the energy and synthetic machinery and

4510-632: The genome also increases the vulnerability of DNA to damage. RNA polymerase plays a very crucial role in all steps including post-transcriptional changes in RNA. As shown in the image in the right it is evident that the CTD (C Terminal Domain) is a tail that changes its shape; this tail will be used as a carrier of splicing, capping and polyadenylation , as shown in the image on the left. Transcription inhibitors can be used as antibiotics against, for example, pathogenic bacteria ( antibacterials ) and fungi ( antifungals ). An example of such an antibacterial

4592-424: The genome that are major gene-regulatory elements. Enhancers control cell-type-specific gene transcription programs, most often by looping through long distances to come in physical proximity with the promoters of their target genes. While there are hundreds of thousands of enhancer DNA regions, for a particular type of tissue only specific enhancers are brought into proximity with the promoters that they regulate. In

4674-406: The host nucleus before it is able to replicate. Some of these viruses require host cell polymerases to replicate their genome , while others, such as adenoviruses or herpes viruses, encode their own replication factors. However, in either case, replication of the viral genome is highly dependent on a cellular state permissive to DNA replication and, thus, on the cell cycle . The virus may induce

4756-402: The host cell undergoes programmed cell death, or apoptosis , of T cells . However, in other retroviruses, the host cell remains intact as the virus buds out of the cell. Viral replication Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through

4838-449: The host via fusion or cell-cell fusion. Viruses attach to proteins on the host cell surface known as cellular receptors or attachment factors to aid entry. Evidence shows that viruses utilize ion channels on the host cells during viral entry. Fusion: External viral proteins promote the fusion of the virion with the plasma membrane. This forms a pore in the host membrane, and after entry, the virion becomes uncoated, and its genomic material

4920-581: The key subunit, TBP , is an ortholog of archaeal TBP), TFIIE (an ortholog of archaeal TFE), TFIIF , and TFIIH . The TFIID is the first component to bind to DNA due to binding of TBP, while TFIIH is the last component to be recruited. In archaea and eukaryotes, the RNA polymerase-promoter closed complex is usually referred to as the " preinitiation complex ". Transcription initiation is regulated by additional proteins, known as activators and repressors , and, in some cases, associated coactivators or corepressors , which modulate formation and function of

5002-401: The low-molecular-weight precursors for the synthesis of viral proteins and nucleic acids. Virus replication occurs in seven stages: It is the first step of viral replication. Some viruses attach to the cell membrane of the host cell and inject its DNA or RNA into the host to initiate infection. Attachment to a host cell is often achieved by a virus attachment protein that extends from

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5084-540: The mRNA, thus releasing the newly synthesized mRNA from the elongation complex. Transcription termination in eukaryotes is less well understood than in bacteria, but involves cleavage of the new transcript followed by template-independent addition of adenines at its new 3' end, in a process called polyadenylation . Beyond termination by a terminator sequences (which is a part of a gene ), transcription may also need to be terminated when it encounters conditions such as DNA damage or an active replication fork . In bacteria,

5166-463: The newly synthesized RNA molecule forms a G-C-rich hairpin loop followed by a run of Us. When the hairpin forms, the mechanical stress breaks the weak rU-dA bonds, now filling the DNA–RNA hybrid. This pulls the poly-U transcript out of the active site of the RNA polymerase, terminating transcription. In Rho-dependent termination, Rho , a protein factor, destabilizes the interaction between the template and

5248-413: The nucleoplasm of a HeLa cell , among which are ~8,000 polymerase II factories and ~2,000 polymerase III factories. Each polymerase II factory contains ~8 polymerases. As most active transcription units are associated with only one polymerase, each factory usually contains ~8 different transcription units. These units might be associated through promoters and/or enhancers, with loops forming a "cloud" around

5330-413: The open complex, the promoter DNA is partly unwound and single-stranded. The exposed, single-stranded DNA is referred to as the "transcription bubble". RNA polymerase, assisted by one or more general transcription factors, then selects a transcription start site in the transcription bubble, binds to an initiating NTP and an extending NTP (or a short RNA primer and an extending NTP) complementary to

5412-433: The pleiotropic effect typical of Hfq deletion strains. Electron microscopy imaging reveals that, in addition to the expected localization of this protein in cytoplasmic regions and in the nucleoid, an important fraction of Hfq is located in close proximity to the membrane. Six crystallographic structures of 4 different Hfq proteins have been published so far; E. coli Hfq ( PDB : 1HK9 ​), P. aeruginosa Hfq in

5494-649: The previous section, transcription factors are proteins that bind to specific DNA sequences in order to regulate the expression of a gene. The binding sequence for a transcription factor in DNA is usually about 10 or 11 nucleotides long. As summarized in 2009, Vaquerizas et al. indicated there are approximately 1,400 different transcription factors encoded in the human genome by genes that constitute about 6% of all human protein encoding genes. About 94% of transcription factor binding sites (TFBSs) that are associated with signal-responsive genes occur in enhancers while only about 6% of such TFBSs occur in promoters. EGR1 protein

5576-475: The product of a classical immediate-early gene and, for instance, it is robustly and transiently produced after neuronal activation. Where the DNA methyltransferase isoform DNMT3A2 binds and adds methyl groups to cytosines appears to be determined by histone post translational modifications. On the other hand, neural activation causes degradation of DNMT3A1 accompanied by reduced methylation of at least one evaluated targeted promoter. Transcription begins with

5658-418: The promoter of a target gene. The loop is stabilized by a dimer of a connector protein (e.g. dimer of CTCF or YY1 ), with one member of the dimer anchored to its binding motif on the enhancer and the other member anchored to its binding motif on the promoter (represented by the red zigzags in the illustration). Several cell function specific transcription factors (there are about 1,600 transcription factors in

5740-424: The protein shell ( capsid ), of a virus. This protein is responsible for binding to a surface receptor on the plasma membrane (or membrane carbohydrates) of a host cell. Viruses can exploit normal cell receptor functions to allow attachment to occur by mimicking molecules that bind to host cell receptors. For example, the rhinovirus uses their virus attachment protein to bind to the receptor ICAM-1 on host cells that

5822-401: The replication enzymes in the host cell nucleus to replicate the viral genome. Many RNA viruses typically replicate in the cytosol , and can directly access the host cell's ribosomes to manufacture viral proteins once the RNA is in a replicative form. Viruses may undergo two types of life cycles: the lytic cycle and the lysogenic cycle. In the lytic cycle, the virus introduces its genome into

5904-510: The reverse transcriptase protein that often comes with the RNA virus can be used as an indirect target for RNA viruses, preventing transcription and synthesis of viral particles. (This is the basis for anti-AIDs and anti-HIV drugs ) Like most viruses with RNA genomes, double-stranded RNA viruses do not rely on host polymerases for replication to the extent that viruses with DNA genomes do. Double-stranded RNA viruses are not as well-studied as other classes. This class includes two major families,

5986-501: The same area that viral transcription occurs. Different viruses have various mechanisms for uncoating. Some RNA viruses such as Rhinoviruses use the low pH in a host cell's endosomes to activate their uncoating mechanism. This involves the rhinovirus releasing a protein that creates holes in the endosome, and allows the virus to release its genome through the holes. Many DNA viruses travel to the host cells nucleus and release their genetic material through nuclear pores. The fourth step in

6068-465: The substitution of uracil for thymine). This is the strand that is used by convention when presenting a DNA sequence. Transcription has some proofreading mechanisms, but they are fewer and less effective than the controls for copying DNA. As a result, transcription has a lower copying fidelity than DNA replication. Transcription is divided into initiation , promoter escape , elongation, and termination . Setting up for transcription in mammals

6150-431: The transcription initiation complex. After the first bond is synthesized, the RNA polymerase must escape the promoter. During this time there is a tendency to release the RNA transcript and produce truncated transcripts. This is called abortive initiation , and is common for both eukaryotes and prokaryotes. Abortive initiation continues to occur until an RNA product of a threshold length of approximately 10 nucleotides

6232-456: The transcription start site sequence, and catalyzes bond formation to yield an initial RNA product. In bacteria , RNA polymerase holoenzyme consists of five subunits: 2 α subunits, 1 β subunit, 1 β' subunit, and 1 ω subunit. In bacteria, there is one general RNA transcription factor known as a sigma factor . RNA polymerase core enzyme binds to the bacterial general transcription (sigma) factor to form RNA polymerase holoenzyme and then binds to

6314-513: The transcription start sites. These include enhancers , silencers , insulators and tethering elements. Among this constellation of elements, enhancers and their associated transcription factors have a leading role in the initiation of gene transcription. An enhancer localized in a DNA region distant from the promoter of a gene can have a very large effect on gene transcription, with some genes undergoing up to 100-fold increased transcription due to an activated enhancer. Enhancers are regions of

6396-416: The two DNA strands serves as a template for transcription. The antisense strand of DNA is read by RNA polymerase from the 3' end to the 5' end during transcription (3' → 5'). The complementary RNA is created in the opposite direction, in the 5' → 3' direction, matching the sequence of the sense strand except switching uracil for thymine. This directionality is because RNA polymerase can only add nucleotides to

6478-433: The viral cycle is replication, which is defined by the rapid production of the viral genome. How a virus undergoes replication relies on the type of genetic material the virus possesses. Based on their genetic material, viruses will hijack the corresponding cellular machinery for said genetic material. Viruses that contain double-stranded DNA (dsDNA) share the same kind of genetic material as all organisms, and can therefore use

6560-477: The virus is no longer attached to the host cell. Another common way viruses leave the host cell is through cell lysis , where the viruses lyse the cell causing it to burst which releases mature viruses that were in the host cell. Viruses are split into seven classes, according to the type of genetic material and method of mRNA production, each of which has its own families of viruses, which in turn have differing replication strategies themselves. David Baltimore ,

6642-459: Was established in vitro by several laboratories by 1965; however, the RNA synthesized by these enzymes had properties that suggested the existence of an additional factor needed to terminate transcription correctly. Roger D. Kornberg won the 2006 Nobel Prize in Chemistry "for his studies of the molecular basis of eukaryotic transcription ". Transcription can be measured and detected in

6724-420: Was found in mRNAs and sRNAs. In Photorhabdus luminescens , a deletion of the hfq gene causes loss of secondary metabolite production. Hfq mediates its pleiotropic effects through several mechanisms. It interacts with regulatory sRNA and facilitates their antisense interaction with their targets. It also acts independently to modulate mRNA decay (directing mRNA transcripts for degradation) and also acts as

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