78-519: See text Iflaviridae is a family of positive sense RNA viruses insect -infecting viruses . Some of the insects commonly infected by iflaviruses include aphids , leafhoppers , flies , bees , ants , silkworms and wasps . The name "Ifla" is derived from the name " I nfectious fla cherie virus", a member species. There is one genus ( Iflavirus ) and 16 species in this family. Members of this family are insect-infecting viruses that consist of positive single-strand RNA genomes translated into
156-543: A +ve RNA ancestor and the -ve RNA viruses from within the dsRNA viruses. The closest relation to the -ve stranded RNA viruses is the Reoviridae . This is the single largest group of RNA viruses and has been organized by the ICTV into the phyla Kitrinoviricota , Lenarviricota , and Pisuviricota in the kingdom Orthornavirae and realm Riboviria . Positive-strand RNA viruses can also be classified based on
234-459: A cell to make a protein, which in turn could directly treat a disease or could function as a vaccine ; more indirectly the protein could drive an endogenous stem cell to differentiate in a desired way. The primary challenges of RNA therapy center on delivering the RNA to the appropriate cells. Challenges include the fact that naked RNA sequences naturally degrade after preparation; they may trigger
312-473: A combination of cis-regulatory sequences on the RNA and trans-acting RNA-binding proteins. Poly(A) tail removal is thought to disrupt the circular structure of the message and destabilize the cap binding complex . The message is then subject to degradation by either the exosome complex or the decapping complex . In this way, translationally inactive messages can be destroyed quickly, while active messages remain intact. The mechanism by which translation stops and
390-625: A complex known as the RNA-induced silencing complex or RISC. This complex contains an endonuclease that cleaves perfectly complementary messages to which the siRNA binds. The resulting mRNA fragments are then destroyed by exonucleases . siRNA is commonly used in laboratories to block the function of genes in cell culture. It is thought to be part of the innate immune system as a defense against double-stranded RNA viruses. MicroRNAs (miRNAs) are small RNAs that typically are partially complementary to sequences in metazoan messenger RNAs. Binding of
468-566: A form of recombination. Recombination also occurs in the Reoviridae (dsRNA), e.g. reovirus; Orthomyxoviridae ((-)ssRNA), e.g. influenza virus ; and Coronaviridae ((+)ssRNA), e.g. SARS . Recombination in RNA viruses appears to be an adaptation for coping with genome damage. Recombination can occur infrequently between animal viruses of the same species but of divergent lineages. The resulting recombinant viruses may sometimes cause an outbreak of infection in humans. Classification
546-565: A gene is cleaved at the poly-A addition site, and 100–200 A's are added to the 3' end of the RNA. If this site is altered, an abnormally long and unstable mRNA construct will be formed. Another difference between eukaryotes and prokaryotes is mRNA transport. Because eukaryotic transcription and translation is compartmentally separated, eukaryotic mRNAs must be exported from the nucleus to the cytoplasm —a process that may be regulated by different signaling pathways. Mature mRNAs are recognized by their processed modifications and then exported through
624-412: A key characteristic for accurate reference-free viral classification. There are three distinct groups of RNA viruses depending on their genome and mode of replication: Retroviruses (Group VI) have a single-stranded RNA genome but, in general, are not considered RNA viruses because they use DNA intermediates to replicate. Reverse transcriptase , a viral enzyme that comes from the virus itself after it
702-433: A miRNA to a message can repress translation of that message and accelerate poly(A) tail removal, thereby hastening mRNA degradation. The mechanism of action of miRNAs is the subject of active research. There are other ways by which messages can be degraded, including non-stop decay and silencing by Piwi-interacting RNA (piRNA), among others. The administration of a nucleoside-modified messenger RNA sequence can cause
780-416: A number of key viral proteins and virion capsids of several dsRNA viruses, highlighting the significant parallels in the structure and replicative processes of many of these viruses. RNA viruses generally have very high mutation rates compared to DNA viruses , because viral RNA polymerases lack the proofreading ability of DNA polymerases . The genetic diversity of RNA viruses is one reason why it
858-579: A number of unassigned genera and species recognised in this group. There are three orders and 34 families recognised in this group. In addition, there are a number of unclassified species and genera. Satellite viruses An unclassified astrovirus/hepevirus-like virus has also been described. With the exception of the Hepatitis D virus , this group of viruses has been placed into a single phylum— Negarnaviricota . This phylum has been divided into two subphyla— Haploviricotina and Polyploviricotina . Within
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#1732801983221936-425: A single polyprotein of ~3000 amino acids long. It encodes helicase , protease and RNA-dependent RNA polymerase enzymes and four structural proteins (VP1–4). The non-enveloped capsid has an icosahedral T=pseudo3 symmetry and is around 30 nm in diameter. VP1, VP2 and VP3 form the outer portion, with VP4 located internally. Genomes are linear and non-segmented, around 8.8-9.7kb in length. Viral replication
1014-429: Is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene , and is read by a ribosome in the process of synthesizing a protein . mRNA is created during the process of transcription , where an enzyme ( RNA polymerase ) converts the gene into primary transcript mRNA (also known as pre-mRNA ). This pre-mRNA usually still contains introns , regions that will not go on to code for
1092-417: Is at polyribosomes selectively localized beneath synapses. The mRNA for Arc/Arg3.1 is induced by synaptic activity and localizes selectively near active synapses based on signals generated by NMDA receptors . Other mRNAs also move into dendrites in response to external stimuli, such as β-actin mRNA. For export from the nucleus, actin mRNA associates with ZBP1 and later with 40S subunit . The complex
1170-541: Is based principally on the type of genome (double-stranded, negative- or positive-single-strand) and gene number and organization. Currently, there are 5 orders and 47 families of RNA viruses recognized. There are also many unassigned species and genera. Related to but distinct from the RNA viruses are the viroids and the RNA satellite viruses . These are not currently classified as RNA viruses and are described on their own pages. A study of several thousand RNA viruses has shown
1248-599: Is bound by a motor protein and is transported to the target location ( neurite extension ) along the cytoskeleton . Eventually ZBP1 is phosphorylated by Src in order for translation to be initiated. In developing neurons, mRNAs are also transported into growing axons and especially growth cones. Many mRNAs are marked with so-called "zip codes", which target their transport to a specific location. mRNAs can also transfer between mammalian cells through structures called tunneling nanotubes . Because prokaryotic mRNA does not need to be processed or transported, translation by
1326-716: Is cytoplasmic. Entry into the host cell is achieved by attachment to host receptors, which mediates endocytosis. Replication follows the positive stranded RNA virus replication model. Positive stranded RNA virus transcription is the method of transcription. Translation takes place by ribosomal skipping. Insects serve as the natural host. Several viruses in this family are economically important because they are highly pathogenic to their honeybee and silkworm hosts, while others (including Dinocampus coccinellae paralysis virus , Nasonia vitripennis virus and Venturia canescens picorna-like virus ) appear to cause little or no symptoms. The family Iflaviridae contains one genus, Iflavirus , with
1404-450: Is difficult to make effective vaccines against them. Retroviruses also have a high mutation rate even though their DNA intermediate integrates into the host genome (and is thus subject to host DNA proofreading once integrated), because errors during reverse transcription are embedded into both strands of DNA before integration. Some genes of RNA virus are important to the viral replication cycles and mutations are not tolerated. For example,
1482-605: Is not infectious by itself as it needs to be transcribed into positive-sense RNA; each virion can be transcribed to several positive-sense RNAs. Ambisense RNA viruses resemble negative-sense RNA viruses, except they translate genes from their negative and positive strands. The double-stranded (ds)RNA viruses represent a diverse group of viruses that vary widely in host range (humans, animals, plants, fungi , and bacteria ), genome segment number (one to twelve), and virion organization ( Triangulation number , capsid layers, spikes, turrets, etc.). Members of this group include
1560-419: Is similar to mRNA and thus can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA-dependent RNA polymerase before translation. Purified RNA of a positive-sense virus can directly cause infection though it may be less infectious than the whole virus particle. In contrast, purified RNA of a negative-sense virus
1638-635: Is termed mature mRNA . mRNA uses uracil (U) instead of thymine (T) in DNA. uracil (U) is the complementary base to adenine (A) during transcription instead of thymine (T). Thus, when using a template strand of DNA to build RNA, thymine is replaced with uracil. This substitution allows the mRNA to carry the appropriate genetic information from DNA to the ribosome for translation. Regarding the natural history, uracil came first then thymine; evidence suggests that RNA came before DNA in evolution. The RNA World hypothesis proposes that life began with RNA molecules, before
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#17328019832211716-486: Is the apolipoprotein B mRNA, which is edited in some tissues, but not others. The editing creates an early stop codon, which, upon translation, produces a shorter protein. Polyadenylation is the covalent linkage of a polyadenylyl moiety to a messenger RNA molecule. In eukaryotic organisms most messenger RNA (mRNA) molecules are polyadenylated at the 3' end, but recent studies have shown that short stretches of uridine (oligouridylation) are also common. The poly(A) tail and
1794-431: Is the case for most of the eukaryotic mRNAs. On the other hand, polycistronic mRNA carries several open reading frames (ORFs), each of which is translated into a polypeptide. These polypeptides usually have a related function (they often are the subunits composing a final complex protein) and their coding sequence is grouped and regulated together in a regulatory region, containing a promoter and an operator . Most of
1872-410: Is uncoated, converts the viral RNA into a complementary strand of DNA, which is copied to produce a double-stranded molecule of viral DNA. After this DNA is integrated into the host genome using the viral enzyme integrase , expression of the encoded genes may lead to the formation of new virions. Numerous RNA viruses are capable of genetic recombination when at least two viral genomes are present in
1950-673: Is viruses that use a homologous RNA-dependent polymerase for replication, are categorized by the International Committee on Taxonomy of Viruses (ICTV) into the realm Riboviria . This includes RNA viruses belonging to Group III , Group IV or Group V of the Baltimore classification system as well as Group VI. Group VI viruses are retroviruses , viruses with RNA genetic material that use DNA intermediates in their life cycle including HIV-1 and HIV-2 which cause AIDS . The majority of such RNA viruses fall into
2028-598: The California Institute of Technology for assistance. During the summer of 1960, Brenner, Jacob, and Meselson conducted an experiment in Meselson's laboratory at Caltech which was the first to prove the existence of mRNA. That fall, Jacob and Monod coined the name "messenger RNA" and developed the first theoretical framework to explain its function. In February 1961, James Watson revealed that his Harvard -based research group had been right behind them with
2106-542: The central dogma of molecular biology , which describes the flow of genetic information in a biological system. As in DNA , genetic information in mRNA is contained in the sequence of nucleotides , which are arranged into codons consisting of three ribonucleotides each. Each codon codes for a specific amino acid , except the stop codons , which terminate protein synthesis. The translation of codons into amino acids requires two other types of RNA: transfer RNA, which recognizes
2184-445: The endoplasmic reticulum by the signal recognition particle . Therefore, unlike in prokaryotes, eukaryotic translation is not directly coupled to transcription. It is even possible in some contexts that reduced mRNA levels are accompanied by increased protein levels, as has been observed for mRNA/protein levels of EEF1A1 in breast cancer . Coding regions are composed of codons , which are decoded and translated into proteins by
2262-487: The eukaryotic initiation factors eIF-4E and eIF-4G , and poly(A)-binding protein . eIF-4E and eIF-4G block the decapping enzyme ( DCP2 ), and poly(A)-binding protein blocks the exosome complex , protecting the ends of the message. The balance between translation and decay is reflected in the size and abundance of cytoplasmic structures known as P-bodies . The poly(A) tail of the mRNA is shortened by specialized exonucleases that are targeted to specific messenger RNAs by
2340-404: The nuclear pore by binding to the cap-binding proteins CBP20 and CBP80, as well as the transcription/export complex (TREX). Multiple mRNA export pathways have been identified in eukaryotes. In spatially complex cells, some mRNAs are transported to particular subcellular destinations. In mature neurons , certain mRNA are transported from the soma to dendrites . One site of mRNA translation
2418-418: The pre-mRNA as exonic splicing enhancers or exonic splicing silencers . Untranslated regions (UTRs) are sections of the mRNA before the start codon and after the stop codon that are not translated, termed the five prime untranslated region (5' UTR) and three prime untranslated region (3' UTR), respectively. These regions are transcribed with the coding region and thus are exonic as they are present in
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2496-406: The ribosome can begin immediately after the end of transcription. Therefore, it can be said that prokaryotic translation is coupled to transcription and occurs co-transcriptionally . Eukaryotic mRNA that has been processed and transported to the cytoplasm (i.e., mature mRNA) can then be translated by the ribosome. Translation may occur at ribosomes free-floating in the cytoplasm, or directed to
2574-417: The rotaviruses , which are the most common cause of gastroenteritis in young children, and picobirnaviruses , which are the most common virus in fecal samples of both humans and animals with or without signs of diarrhea. Bluetongue virus is an economically important pathogen that infects cattle and sheep. In recent years, progress has been made in determining atomic and subnanometer resolution structures of
2652-434: The "front" or 5' end of a eukaryotic messenger RNA shortly after the start of transcription. The 5' cap consists of a terminal 7-methylguanosine residue that is linked through a 5'-5'-triphosphate bond to the first transcribed nucleotide. Its presence is critical for recognition by the ribosome and protection from RNases . Cap addition is coupled to transcription, and occurs co-transcriptionally, such that each influences
2730-769: The 'typovirus' group (apple chlorotic leaf spot virus, carlaviruses, potexviruses and tymoviruses). The alpha like supergroup can be further divided into three clades : the rubi-like, tobamo-like, and tymo-like viruses. Additional work has identified five groups of positive-stranded RNA viruses containing four, three, three, three, and one order(s), respectively. These fourteen orders contain 31 virus families (including 17 families of plant viruses) and 48 genera (including 30 genera of plant viruses). This analysis suggests that alphaviruses and flaviviruses can be separated into two families—the Togaviridae and Flaviridae, respectively—but suggests that other taxonomic assignments, such as
2808-418: The 1990s, mRNA vaccines for personalized cancer have been developed, relying on non-nucleoside modified mRNA. mRNA based therapies continue to be investigated as a method of treatment or therapy for both cancer as well as auto-immune, metabolic, and respiratory inflammatory diseases. Gene editing therapies such as CRISPR may also benefit from using mRNA to induce cells to make the desired Cas protein. Since
2886-572: The 2010s, RNA vaccines and other RNA therapeutics have been considered to be "a new class of drugs". The first mRNA-based vaccines received restricted authorization and were rolled out across the world during the COVID-19 pandemic by Pfizer–BioNTech COVID-19 vaccine and Moderna , for example. The 2023 Nobel Prize in Physiology or Medicine was awarded to Katalin Karikó and Drew Weissman for
2964-408: The 5' UTR and/or 3' UTR due to varying affinity for RNA degrading enzymes called ribonucleases and for ancillary proteins that can promote or inhibit RNA degradation. (See also, C-rich stability element .) Translational efficiency, including sometimes the complete inhibition of translation, can be controlled by UTRs. Proteins that bind to either the 3' or 5' UTR may affect translation by influencing
3042-505: The Potexviridae. The evolution of the picornaviruses based on an analysis of their RNA polymerases and helicases appears to date to the divergence of eukaryotes . Their putative ancestors include the bacterial group II retroelements , the family of HtrA proteases and DNA bacteriophages . Partitiviruses are related to and may have evolved from a totivirus ancestor. Hypoviruses and barnaviruses appear to share an ancestry with
3120-507: The RNA-dependent RNA polymerase. Three groups have been recognised: A division of the alpha-like (Sindbis-like) supergroup on the basis of a novel domain located near the N termini of the proteins involved in viral replication has been proposed. The two groups proposed are: the 'altovirus' group (alphaviruses, furoviruses, hepatitis E virus, hordeiviruses, tobamoviruses, tobraviruses, tricornaviruses and probably rubiviruses); and
3198-500: The assistance of another virus to complete their life cycle—are also known. Their taxonomy has yet to be settled. The following four genera have been proposed for positive sense single stranded RNA satellite viruses that infect plants— Albetovirus , Aumaivirus , Papanivirus and Virtovirus . A family— Sarthroviridae which includes the genus Macronovirus —has been proposed for the positive sense single stranded RNA satellite viruses that infect arthropods . There are twelve families and
Iflaviridae - Misplaced Pages Continue
3276-430: The body's immune system to attack them as an invader; and they are impermeable to the cell membrane . Once within the cell, they must then leave the cell's transport mechanism to take action within the cytoplasm , which houses the necessary ribosomes . Overcoming these challenges, mRNA as a therapeutic was first put forward in 1989 "after the development of a broadly applicable in vitro transfection technique." In
3354-461: The codon and provides the corresponding amino acid, and ribosomal RNA (rRNA), the central component of the ribosome's protein-manufacturing machinery. The concept of mRNA was developed by Sydney Brenner and Francis Crick in 1960 during a conversation with François Jacob . In 1961, mRNA was identified and described independently by one team consisting of Brenner, Jacob, and Matthew Meselson , and another team led by James Watson . While analyzing
3432-417: The cytoplasm and its translation by the ribosome. The extensive processing of eukaryotic pre-mRNA that leads to the mature mRNA is the RNA splicing , a mechanism by which introns or outrons (non-coding regions) are removed and exons (coding regions) are joined. A 5' cap (also termed an RNA cap, an RNA 7-methylguanosine cap, or an RNA m G cap) is a modified guanine nucleotide that has been added to
3510-462: The data in preparation for publication, Jacob and Jacques Monod coined the name "messenger RNA". The brief existence of an mRNA molecule begins with transcription, and ultimately ends in degradation. During its life, an mRNA molecule may also be processed, edited, and transported prior to translation. Eukaryotic mRNA molecules often require extensive processing and transport, while prokaryotic mRNA molecules do not. A molecule of eukaryotic mRNA and
3588-521: The destruction of an mRNA, some of which are described below. In general, in prokaryotes the lifetime of mRNA is much shorter than in eukaryotes. Prokaryotes degrade messages by using a combination of ribonucleases, including endonucleases , 3' exonucleases , and 5' exonucleases. In some instances, small RNA molecules (sRNA) tens to hundreds of nucleotides long can stimulate the degradation of specific mRNAs by base-pairing with complementary sequences and facilitating ribonuclease cleavage by RNase III . It
3666-400: The development of effective mRNA vaccines against COVID-19. Several molecular biology studies during the 1950s indicated that RNA played some kind of role in protein synthesis, but that role was not clearly understood. For instance, in one of the earliest reports, Jacques Monod and his team showed that RNA synthesis was necessary for protein synthesis, specifically during the production of
3744-469: The elements contained in untranslated regions form a characteristic secondary structure when transcribed into RNA. These structural mRNA elements are involved in regulating the mRNA. Some, such as the SECIS element , are targets for proteins to bind. One class of mRNA element, the riboswitches , directly bind small molecules, changing their fold to modify levels of transcription or translation. In these cases,
3822-476: The emergence of DNA genomes and coded proteins. In DNA, the evolutionary substitution of thymine for uracil may have increased DNA stability and improved the efficiency of DNA replication. Processing of mRNA differs greatly among eukaryotes , bacteria , and archaea . Non-eukaryotic mRNA is, in essence, mature upon transcription and requires no processing, except in rare cases. Eukaryotic pre-mRNA, however, requires several processing steps before its transport to
3900-404: The enzyme β-galactosidase in the bacterium E. coli . Arthur Pardee also found similar RNA accumulation in 1954 . In 1953, Alfred Hershey , June Dixon, and Martha Chase described a certain cytosine-containing DNA (indicating it was RNA) that disappeared quickly after its synthesis in E. coli . In hindsight, this may have been one of the first observations of the existence of mRNA but it
3978-477: The families Caliciviridae , Flaviviridae , and Picornaviridae and a second that includes the families Alphatetraviridae , Birnaviridae , Cystoviridae , Nodaviridae , and Permutotretraviridae . These viruses have multiple types of genome ranging from a single RNA molecule up to eight segments. Despite their diversity it appears that they may have originated in arthropods and to have diversified from there. A number of satellite viruses—viruses that require
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#17328019832214056-403: The final amino acid sequence . These are removed in the process of RNA splicing , leaving only exons , regions that will encode the protein. This exon sequence constitutes mature mRNA . Mature mRNA is then read by the ribosome, and the ribosome creates the protein utilizing amino acids carried by transfer RNA (tRNA). This process is known as translation . All of these processes form part of
4134-508: The following 16 species: RNA virus#Group IV—positive-sense ssRNA viruses An RNA virus is a virus characterized by a ribonucleic acid ( RNA ) based genome . The genome can be single-stranded RNA ( ssRNA ) or double-stranded (dsRNA). Notable human diseases caused by RNA viruses include influenza , SARS , MERS , COVID-19 , Dengue virus , hepatitis C , hepatitis E , West Nile fever , Ebola virus disease , rabies , polio , mumps , and measles . All known RNA viruses, that
4212-453: The kingdom Orthornavirae and the rest have a positioning not yet defined . The realm does not contain all RNA viruses: Deltavirus , Avsunviroidae , and Pospiviroidae are taxa of RNA viruses that were mistakenly included in 2019, but corrected in 2020. RNA viruses can be further classified according to the sense or polarity of their RNA into negative-sense and positive-sense , or ambisense RNA viruses. Positive-sense viral RNA
4290-419: The lifetime averages between 1 and 3 minutes, making bacterial mRNA much less stable than eukaryotic mRNA. In mammalian cells, mRNA lifetimes range from several minutes to days. The greater the stability of an mRNA the more protein may be produced from that mRNA. The limited lifetime of mRNA enables a cell to alter protein synthesis rapidly in response to its changing needs. There are many mechanisms that lead to
4368-448: The mRNA chain is cleaved through the action of an endonuclease complex associated with RNA polymerase. After the mRNA has been cleaved, around 250 adenosine residues are added to the free 3' end at the cleavage site. This reaction is catalyzed by polyadenylate polymerase . Just as in alternative splicing , there can be more than one polyadenylation variant of an mRNA. Polyadenylation site mutations also occur. The primary RNA transcript of
4446-418: The mRNA found in bacteria and archaea is polycistronic, as is the human mitochondrial genome. Dicistronic or bicistronic mRNA encodes only two proteins . In eukaryotes mRNA molecules form circular structures due to an interaction between the eIF4E and poly(A)-binding protein , which both bind to eIF4G , forming an mRNA-protein-mRNA bridge. Circularization is thought to promote cycling of ribosomes on
4524-561: The mRNA leading to time-efficient translation, and may also function to ensure only intact mRNA are translated (partially degraded mRNA characteristically have no m7G cap, or no poly-A tail). Other mechanisms for circularization exist, particularly in virus mRNA. Poliovirus mRNA uses a cloverleaf section towards its 5' end to bind PCBP2, which binds poly(A)-binding protein , forming the familiar mRNA-protein-mRNA circle. Barley yellow dwarf virus has binding between mRNA segments on its 5' end and 3' end (called kissing stem loops), circularizing
4602-408: The mRNA regulates itself. The 3' poly(A) tail is a long sequence of adenine nucleotides (often several hundred) added to the 3' end of the pre-mRNA. This tail promotes export from the nucleus and translation, and protects the mRNA from degradation. An mRNA molecule is said to be monocistronic when it contains the genetic information to translate only a single protein chain (polypeptide). This
4680-499: The mRNA without any proteins involved. RNA virus genomes (the + strands of which are translated as mRNA) are also commonly circularized. During genome replication the circularization acts to enhance genome replication speeds, cycling viral RNA-dependent RNA polymerase much the same as the ribosome is hypothesized to cycle. Different mRNAs within the same cell have distinct lifetimes (stabilities). In bacterial cells, individual mRNAs can survive from seconds to more than an hour. However,
4758-528: The mature mRNA. Several roles in gene expression have been attributed to the untranslated regions, including mRNA stability, mRNA localization, and translational efficiency . The ability of a UTR to perform these functions depends on the sequence of the UTR and can differ between mRNAs. Genetic variants in 3' UTR have also been implicated in disease susceptibility because of the change in RNA structure and protein translation. The stability of mRNAs may be controlled by
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#17328019832214836-435: The message is handed-off to decay complexes is not understood in detail. The majority of mRNA decay was believed to be cytoplasmic; however, recently, a novel mRNA decay pathway was described, which starts in the nucleus. The presence of AU-rich elements in some mammalian mRNAs tends to destabilize those transcripts through the action of cellular proteins that bind these sequences and stimulate poly(A) tail removal. Loss of
4914-460: The new mRNA strand to become double stranded by producing a complementary strand known as the tRNA strand, which when combined are unable to form structures from base-pairing. Moreover, the template for mRNA is the complementary strand of tRNA, which is identical in sequence to the anticodon sequence that the DNA binds to. The short-lived, unprocessed or partially processed product is termed precursor mRNA , or pre-mRNA ; once completely processed, it
4992-442: The other. Shortly after the start of transcription, the 5' end of the mRNA being synthesized is bound by a cap-synthesizing complex associated with RNA polymerase . This enzymatic complex catalyzes the chemical reactions that are required for mRNA capping. Synthesis proceeds as a multi-step biochemical reaction. In some instances, an mRNA will be edited , changing the nucleotide composition of that mRNA. An example in humans
5070-406: The pestiviruses, hepatitis C virus, rubiviruses, hepatitis E virus, and arteriviruses, may be incorrect. The coronaviruses and toroviruses appear to be distinct families in distinct orders and not distinct genera of the same family as currently classified. The luteoviruses appear to be two families rather than one, and apple chlorotic leaf spot virus appears not to be a closterovirus but a new genus of
5148-582: The poly(A) tail is thought to promote mRNA degradation by facilitating attack by both the exosome complex and the decapping complex . Rapid mRNA degradation via AU-rich elements is a critical mechanism for preventing the overproduction of potent cytokines such as tumor necrosis factor (TNF) and granulocyte-macrophage colony stimulating factor (GM-CSF). AU-rich elements also regulate the biosynthesis of proto-oncogenic transcription factors like c-Jun and c-Fos . Eukaryotic messages are subject to surveillance by nonsense-mediated decay (NMD), which checks for
5226-466: The potyvirus and sobemovirus lineages respectively. This analysis also suggests that the dsRNA viruses are not closely related to each other but instead belong to four additional classes—Birnaviridae, Cystoviridae, Partitiviridae, and Reoviridae—and one additional order (Totiviridae) of one of the classes of positive ssRNA viruses in the same subphylum as the positive-strand RNA viruses. One study has suggested that there are two large clades: One includes
5304-412: The presence of at least five main taxa: a levivirus and relatives group; a picornavirus supergroup; an alphavirus supergroup plus a flavivirus supergroup; the dsRNA viruses; and the -ve strand viruses. The lentivirus group appears to be basal to all the remaining RNA viruses. The next major division lies between the picornasupragroup and the remaining viruses. The dsRNA viruses appear to have evolved from
5382-516: The presence of premature stop codons (nonsense codons) in the message. These can arise via incomplete splicing, V(D)J recombination in the adaptive immune system , mutations in DNA, transcription errors, leaky scanning by the ribosome causing a frame shift , and other causes. Detection of a premature stop codon triggers mRNA degradation by 5' decapping, 3' poly(A) tail removal, or endonucleolytic cleavage . In metazoans , small interfering RNAs (siRNAs) processed by Dicer are incorporated into
5460-474: The protein bound to it aid in protecting mRNA from degradation by exonucleases. Polyadenylation is also important for transcription termination, export of the mRNA from the nucleus, and translation. mRNA can also be polyadenylated in prokaryotic organisms, where poly(A) tails act to facilitate, rather than impede, exonucleolytic degradation. Polyadenylation occurs during and/or immediately after transcription of DNA into RNA. After transcription has been terminated,
5538-464: The proteins surrounding it are together called a messenger RNP . Transcription is when RNA is copied from DNA. During transcription, RNA polymerase makes a copy of a gene from the DNA to mRNA as needed. This process differs slightly in eukaryotes and prokaryotes. One notable difference is that prokaryotic RNA polymerase associates with DNA-processing enzymes during transcription so that processing can proceed during transcription. Therefore, this causes
5616-434: The region of the hepatitis C virus genome that encodes the core protein is highly conserved , because it contains an RNA structure involved in an internal ribosome entry site . On average, dsRNA viruses show a lower sequence redundancy relative to ssRNA viruses. Contrarily, dsDNA viruses contain the most redundant genome sequences while ssDNA viruses have the least. The sequence complexity of viruses has been shown to be
5694-438: The ribosome's ability to bind to the mRNA. MicroRNAs bound to the 3' UTR also may affect translational efficiency or mRNA stability. Cytoplasmic localization of mRNA is thought to be a function of the 3' UTR. Proteins that are needed in a particular region of the cell can also be translated there; in such a case, the 3' UTR may contain sequences that allow the transcript to be localized to this region for translation. Some of
5772-467: The ribosome; in eukaryotes usually into one and in prokaryotes usually into several. Coding regions begin with the start codon and end with a stop codon . In general, the start codon is an AUG triplet and the stop codon is UAG ("amber"), UAA ("ochre"), or UGA ("opal"). The coding regions tend to be stabilised by internal base pairs; this impedes degradation. In addition to being protein-coding, portions of coding regions may serve as regulatory sequences in
5850-460: The same host cell. Very rarely viral RNA can recombine with host RNA. RNA recombination appears to be a major driving force in determining genome architecture and the course of viral evolution among Picornaviridae ( (+)ssRNA ), e.g. poliovirus . In the Retroviridae ((+)ssRNA), e.g. HIV , damage in the RNA genome appears to be avoided during reverse transcription by strand switching,
5928-491: The subphylum Haploviricotina four classes are currently recognised: Chunqiuviricetes , Milneviricetes , Monjiviricetes and Yunchangviricetes . In the subphylum Polyploviricotina two classes are recognised: Ellioviricetes and Insthoviricetes . Six classes, seven orders and twenty four families are currently recognized in this group. A number of unassigned species and genera are yet to be classified. MRNA In molecular biology , messenger ribonucleic acid ( mRNA )
6006-535: Was not recognized at the time as such. The idea of mRNA was first conceived by Sydney Brenner and Francis Crick on 15 April 1960 at King's College, Cambridge , while François Jacob was telling them about a recent experiment conducted by Arthur Pardee , himself, and Monod (the so-called PaJaMo experiment, which did not prove mRNA existed but suggested the possibility of its existence). With Crick's encouragement, Brenner and Jacob immediately set out to test this new hypothesis, and they contacted Matthew Meselson at
6084-428: Was recently shown that bacteria also have a sort of 5' cap consisting of a triphosphate on the 5' end . Removal of two of the phosphates leaves a 5' monophosphate, causing the message to be destroyed by the exonuclease RNase J, which degrades 5' to 3'. Inside eukaryotic cells, there is a balance between the processes of translation and mRNA decay. Messages that are being actively translated are bound by ribosomes ,
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