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58-522: Betacoronavirus pandemicum (also known as Severe acute respiratory syndrome–related coronavirus , abbreviated as SARSr-CoV or SARS-CoV ) is a species of virus consisting of many known strains. Two strains of the virus have caused outbreaks of severe respiratory diseases in humans: severe acute respiratory syndrome coronavirus 1 (SARS-CoV or SARS-CoV-1), the cause of the 2002–2004 outbreak of severe acute respiratory syndrome (SARS), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),

116-423: A lipid bilayer where the membrane (M), envelope (E) and spike (S) proteins are anchored. The spike proteins provide the virus with its bulbous surface projections, known as peplomers . The spike protein's interaction with its complement host cell receptor is central in determining the tissue tropism , infectivity , and species range of the virus. Inside the envelope, there is the nucleocapsid , which

174-403: A messenger RNA (mRNA) molecule. Each amino acid added is matched to a three-nucleotide subsequence of the mRNA. For each such triplet possible, the corresponding amino acid is accepted. The successive amino acids added to the chain are matched to successive nucleotide triplets in the mRNA. In this way, the sequence of nucleotides in the template mRNA chain determines the sequence of amino acids in

232-413: A chassis for the expression of simple proteins. These strains, such as BL21, are genetically modified to minimize protease activity, hence enabling potential for high efficiency industrial scale protein production . Strains of yeasts are the most common subjects of eukaryotic genetic modification, especially with respect to industrial fermentation . The term has no official ranking status in botany;

290-536: A downstream hairpin (SElenoCysteine Insertion Sequence, or SECIS). There are many computer programs capable of translating a DNA/RNA sequence into a protein sequence. Normally this is performed using the Standard Genetic Code, however, few programs can handle all the "special" cases, such as the use of the alternative initiation codons which are biologically significant. For instance, the rare alternative start codon CTG codes for Methionine when used as

348-483: A more nuanced understanding of how translation regulation can impact cell behavior, metabolic state, and responsiveness to various stimuli or conditions. Translational control is critical for the development and survival of cancer . Cancer cells must frequently regulate the translation phase of gene expression, though it is not fully understood why translation is targeted over steps like transcription. While cancer cells often have genetically altered translation factors, it

406-409: A more recent development is single-cell ribosome profiling, a technique that allows us to study the translation process at the resolution of individual cells. This is particularly significant as cells, even those of the same type, can exhibit considerable variability in their protein synthesis. Single-cell ribosome profiling has the potential to shed light on the heterogeneous nature of cells, leading to

464-457: A polypeptide as the mRNA passes through and is "read" by the ribosome. Translation proceeds in three phases: In prokaryotes (bacteria and archaea), translation occurs in the cytosol, where the large and small subunits of the ribosome bind to the mRNA. In eukaryotes , translation occurs in the cytoplasm or across the membrane of the endoplasmic reticulum in a process called co-translational translocation . In co-translational translocation,

522-402: A protein containing n amino acids, the number of high-energy phosphate bonds required to translate it is 4 n -1. The rate of translation varies; it is significantly higher in prokaryotic cells (up to 17–21 amino acid residues per second) than in eukaryotic cells (up to 6–9 amino acid residues per second). Initiation involves the small subunit of the ribosome binding to the 5' end of mRNA with

580-456: A rice plant, all the descendants of the genetically modified rice plant are a strain with unique genetic information that is passed on to later generations; the strain designation, which is normally a number or a formal name, covers all the plants that descend from the originally modified plant. The rice plants in the strain can be bred to other rice strains or cultivars , and if desirable plants are produced, these are further bred to stabilize

638-480: A set of conserved domains that it shares with the group. Bats serve as the main host reservoir species for the SARS-related coronaviruses like SARS-CoV-1 and SARS-CoV-2. The virus has coevolved in the bat host reservoir over a long period of time. Only recently have strains of SARS-related coronavirus been observed to have evolved into having been able to make the cross-species jump from bats to humans, as in

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696-425: A site for amino acid attachment, and a site called an anticodon. The anticodon is an RNA triplet complementary to the mRNA triplet that codes for their cargo amino acid . Aminoacyl tRNA synthetases ( enzymes ) catalyze the bonding between specific tRNAs and the amino acids that their anticodon sequences call for. The product of this reaction is an aminoacyl-tRNA . The amino acid is joined by its carboxyl group to

754-512: A snapshot of the translatome, showing which parts of the mRNA are being translated into proteins by ribosomes at a given time. Ribosome profiling provides valuable insights into translation dynamics, revealing the complex interplay between gene sequence, mRNA structure, and translation regulation. For example, research utilizing this method has revealed that genetic differences and their subsequent expression as mRNAs can also impact translation rate in an RNA-specific manner. Expanding on this concept,

812-557: A specific amino acid . The ribosome molecules translate this code to a specific sequence of amino acids. The ribosome is a multisubunit structure containing ribosomal RNA (rRNA) and proteins. It is the "factory" where amino acids are assembled into proteins. Transfer RNAs (tRNAs) are small noncoding RNA chains (74–93 nucleotides) that transport amino acids to the ribosome. The repertoire of tRNA genes varies widely between species, with some bacteria having between 20 and 30 genes while complex eukaryotes could have thousands. tRNAs have

870-480: A start codon, and for Leucine in all other positions. Example: Condensed translation table for the Standard Genetic Code (from the NCBI Taxonomy webpage). The "Starts" row indicate three start codons, UUG, CUG, and the very common AUG. It also indicates the first amino acid residue when interpreted as a start: in this case it is all methionine. Even when working with ordinary eukaryotic sequences such as

928-455: A translation into proteins. Several antibiotics act by inhibiting translation. These include anisomycin , cycloheximide , chloramphenicol , tetracycline , streptomycin , erythromycin , and puromycin . Prokaryotic ribosomes have a different structure from that of eukaryotic ribosomes, and thus antibiotics can specifically target bacterial infections without any harm to a eukaryotic host 's cells. The basic process of protein production

986-495: Is a sequence of amino acids . This sequence is determined by the sequence of nucleotides in the RNA. The nucleotides are considered three at a time. Each such triple results in addition of one specific amino acid to the protein being generated. The matching from nucleotide triple to amino acid is called the genetic code . The translation is performed by a large complex of functional RNA and proteins called ribosomes . The entire process

1044-402: Is also possible to translate either by hand (for short sequences) or by computer (after first programming one appropriately, see section below); this allows biologists and chemists to draw out the chemical structure of the encoded protein on paper. First, convert each template DNA base to its RNA complement (note that the complement of A is now U), as shown below. Note that the template strand of

1102-480: Is called gene expression . In translation, messenger RNA (mRNA) is decoded in a ribosome, outside the nucleus, to produce a specific amino acid chain, or polypeptide . The polypeptide later folds into an active protein and performs its functions in the cell. The ribosome facilitates decoding by inducing the binding of complementary transfer RNA (tRNA) anticodon sequences to mRNA codons . The tRNAs carry specific amino acids that are chained together into

1160-437: Is considered genetically identical after 20 generations of sibling-mating. Many rodent strains have been developed for a variety of disease models, and they are also often used to test drug toxicity. The common fruit fly ( Drosophila melanogaster ) was among the first organisms used for genetic analysis , has a simple genome , and is very well understood. It has remained a popular model organism for many other reasons, like

1218-408: Is formed from multiple copies of the nucleocapsid (N) protein, which are bound to the positive-sense single-stranded (~30 kb ) RNA genome in a continuous beads-on-a-string type conformation. The lipid bilayer envelope, membrane proteins, and nucleocapsid protect the virus when it is outside the host. Strain (biology) It has been said that "there is no universally accepted definition for

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1276-421: Is most common species for prokaryotic strain engineering. Scientists have succeeded in establishing viable minimal genomes from which new strains can be developed. These minimal strains provide a near guarantee that experiments on genes outside the minimal framework will not be effected by non-essential pathways. Optimized strains of E. coli are typically used for this application. E. coli are also often used as

1334-491: Is much more common for cancer cells to modify the levels of existing translation factors. Several major oncogenic signaling pathways, including the RAS–MAPK , PI3K/AKT/mTOR , MYC, and WNT–β-catenin pathways, ultimately reprogram the genome via translation. Cancer cells also control translation to adapt to cellular stress. During stress, the cell translates mRNAs that can mitigate the stress and promote survival. An example of this

1392-411: Is the addition of one amino acid at a time to the end of a protein. This operation is performed by a ribosome . A ribosome is made up of two subunits, a small subunit, and a large subunit. These subunits come together before the translation of mRNA into a protein to provide a location for translation to be carried out and a polypeptide to be produced. The choice of amino acid type to add is determined by

1450-400: Is the expression of AMPK in various cancers; its activation triggers a cascade that can ultimately allow the cancer to escape apoptosis (programmed cell death) triggered by nutrition deprivation. Future cancer therapies may involve disrupting the translation machinery of the cell to counter the downstream effects of cancer. The transcription-translation process description, mentioning only

1508-473: The COVID-19 pandemic . SARS-related coronavirus is a member of the genus Betacoronavirus (group 2) and monotypic of the subgenus Sarbecovirus (subgroup B). Sarbecoviruses, unlike embecoviruses or alphacoronaviruses , have only one papain-like proteinase (PLpro) instead of two in the open reading frame ORF1ab . SARSr-CoV was determined to be an early split-off from the betacoronaviruses based on

1566-495: The H5N1 influenza virus. While funding for such research has aroused controversy at times due to safety concerns, leading to a temporary pause, it has subsequently proceeded. In biotechnology, microbial strains have been constructed to establish metabolic pathways suitable for treating a variety of applications. Historically, a major effort of metabolic research has been devoted to the field of biofuel production. Escherichia coli

1624-3252: The accessory proteins , many with no known homologues. The different functions of the accessory proteins are not well understood. SARS coronaviruses have been genetically engineered in several laboratories. Phylogenetic analysis showed that the evolutionary branch composed of Bat coronavirus BtKY72 and BM48-31 was the base group of SARS–related CoVs evolutionary tree, which separated from other SARS–related CoVs earlier than SARS-CoV-1 and SARS-CoV-2. Bat CoV BtKY72 Bat CoV BM48-31 SARS-CoV-1 related coronavirus SARS-CoV-2 related coronavirus A phylogenetic tree based on whole-genome sequences of SARS-CoV-1 and related coronaviruses is: 16BO133 , 86.3% to SARS-CoV-1, Rhinolophus ferrumequinum , North Jeolla , South Korea JTMC15 , 86.4% to SARS-CoV-1, Rhinolophus ferrumequinum , Tonghua , Jilin Bat SARS CoV Rf1, 87.8% to SARS-CoV-1, Rhinolophus ferrumequinum , Yichang , Hubei BtCoV HKU3, 87.9% to SARS-CoV-1, Rhinolophus sinicus , Hong Kong and Guangdong LYRa11 , 90.9% to SARS-CoV-1, Rhinolophus affinis , Baoshan , Yunnan Bat SARS-CoV/Rp3, 92.6% to SARS-CoV-1, Rhinolophus pearsoni , Nanning , Guangxi Bat SL-CoV YNLF_31C, 93.5% to SARS-CoV-1, Rhinolophus ferrumequinum , Lufeng , Yunnan Bat SL-CoV YNLF_34C, 93.5% to SARS-CoV-1, Rhinolophus ferrumequinum , Lufeng , Yunnan SHC014-CoV , 95.4% to SARS-CoV-1, Rhinolophus sinicus , Kunming , Yunnan WIV1 , 95.6% to SARS-CoV-1, Rhinolophus sinicus , Kunming , Yunnan WIV16 , 96.0% to SARS-CoV-1, Rhinolophus sinicus Kunming , Yunnan Civet SARS-CoV , 99.8% to SARS-CoV-1, Paguma larvata , market in Guangdong, China SARS-CoV-1 SARS-CoV-2 , 79% to SARS-CoV-1 A phylogenetic tree based on whole-genome sequences of SARS-CoV-2 and related coronaviruses is: ( Bat ) Rc-o319 , 81% to SARS-CoV-2, Rhinolophus cornutus , Iwate , Japan Bat SL-ZXC21 , 88% to SARS-CoV-2, Rhinolophus pusillus , Zhoushan , Zhejiang Bat SL-ZC45 , 88% to SARS-CoV-2, Rhinolophus pusillus , Zhoushan, Zhejiang Pangolin SARSr-CoV-GX, 85.3% to SARS-CoV-2, Manis javanica , smuggled from Southeast Asia Pangolin SARSr-CoV-GD, 90.1% to SARS-CoV-2, Manis javanica , smuggled from Southeast Asia Bat RshSTT182, 92.6% to SARS-CoV-2, Rhinolophus shameli , Steung Treng , Cambodia Bat RshSTT200, 92.6% to SARS-CoV-2, Rhinolophus shameli , Steung Treng, Cambodia (Bat) RacCS203 , 91.5% to SARS-CoV-2, Rhinolophus acuminatus , Chachoengsao , Thailand (Bat) RmYN02 , 93.3% to SARS-CoV-2, Rhinolophus malayanus , Mengla , Yunnan (Bat) RpYN06 , 94.4% to SARS-CoV-2, Rhinolophus pusillus , Xishuangbanna , Yunnan (Bat) RaTG13 , 96.1% to SARS-CoV-2, Rhinolophus affinis , Mojiang , Yunnan (Bat) BANAL-52 , 96.8% to SARS-CoV-2, Rhinolophus malayanus , Vientiane , Laos SARS-CoV-2 SARS-CoV-1 , 79% to SARS-CoV-2 The morphology of

1682-702: The angiotensin-converting enzyme 2 (ACE2) receptor. The SARSr-CoV species is a member of the genus Betacoronavirus and the only species of the subgenus Sarbecovirus ( SAR S Be ta co rona virus ). The SARS-related coronavirus was one of several viruses identified by the World Health Organization (WHO) in 2016 as a likely cause of a future epidemic in a new plan developed after the Ebola epidemic for urgent research and development before and during an epidemic towards diagnostic tests , vaccines and medicines . This prediction came to pass with

1740-503: The paradigm that "useful models are simple and extendable". The simplest model M0 is represented by the reaction kinetic mechanism (Figure M0). It was generalised to include 40S, 60S and initiation factors (IF) binding (Figure M1'). It was extended further to include effect of microRNA on protein synthesis. Most of models in this hierarchy can be solved analytically. These solutions were used to extract 'kinetic signatures' of different specific mechanisms of synthesis regulation. It

1798-421: The primary structure of the protein. However, proteins tend to fold , depending in part on hydrophilic and hydrophobic segments along the chain. Secondary structure can often still be guessed at, but the proper tertiary structure is often very hard to determine. Whereas other aspects such as the 3D structure, called tertiary structure , of protein can only be predicted using sophisticated algorithms ,

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1856-448: The 3' OH of the tRNA by an ester bond . When the tRNA has an amino acid linked to it, the tRNA is termed "charged". In bacteria, this aminoacyl-tRNA is carried to the ribosome by EF-Tu , where mRNA codons are matched through complementary base pairing to specific tRNA anticodons. Aminoacyl-tRNA synthetases that mispair tRNAs with the wrong amino acids can produce mischarged aminoacyl-tRNAs, which can result in inappropriate amino acids at

1914-465: The 30S ribosomal subunit is bound to the mRNA and is aligned such that the initiation codon is placed in the 30S portion of the P-site. Once the mRNA and 30S subunit are properly bound, an initiation factor brings the initiator tRNA–amino acid complex, f-Met -tRNA, to the 30S P site. The initiation phase is completed once a 50S subunit joins the 30S subunit, forming an active 70S ribosome. Termination of

1972-492: The DNA is the one the RNA is polymerized against; the other DNA strand would be the same as the RNA, but with thymine instead of uracil. Then split the RNA into triplets (groups of three bases). Note that there are 3 translation "windows", or reading frames , depending on where you start reading the code. Finally, use the table at Genetic code to translate the above into a structural formula as used in chemistry. This will give

2030-439: The SARS-related coronavirus is characteristic of the coronavirus family as a whole. The viruses are large pleomorphic spherical particles with bulbous surface projections that form a corona around the particles in electron micrographs. The size of the virus particles is in the 80–90 nm range. The envelope of the virus in electron micrographs appears as a distinct pair of electron dense shells. The viral envelope consists of

2088-399: The amino acid sequence, called primary structure, can be determined solely from the nucleic acid sequence with the aid of a translation table . This approach may not give the correct amino acid composition of the protein, in particular if unconventional amino acids such as selenocysteine are incorporated into the protein, which is coded for by a conventional stop codon in combination with

2146-477: The case of the strains SARS-CoV-1 and SARS-CoV-2 . Both of these strains descended from a single ancestor but made the cross-species jump into humans separately. SARS-CoV-2 is not a direct descendant of SARS-CoV-1. The SARS-related coronavirus is an enveloped, positive-sense, single-stranded RNA virus . Its genome is about 30  kb , which is one of the largest among RNA viruses. The virus has 14 open reading frames which overlap in some cases. The genome has

2204-469: The cause of the pandemic of COVID-19 . There are hundreds of other strains of SARSr-CoV, which are only known to infect non-human mammal species: bats are a major reservoir of many strains of SARSr-CoV; several strains have been identified in Himalayan palm civets , which were likely ancestors of SARS-CoV-1. These enveloped , positive-sense single-stranded RNA viruses enter host cells by binding to

2262-481: The desirable traits; the stabilized plants that can be propagated and "come true" (remain identical to the parent plant) are given a cultivar name and released into production to be used by farmers. A laboratory mouse or rat strain is a group of animals that is genetically uniform. Strains are used in laboratory experiments. Mouse strains can be inbred , mutated , or genetically modified , while rat strains are usually inbred . A given inbred rodent population

2320-448: The ease of its breeding and maintenance, and the speed and volume of its reproduction. Various specific strains have been developed, including a flightless version with stunted wings (also used in the pet trade as live food for small reptiles and amphibians). Translation (biology) In biology , translation is the process in living cells in which proteins are produced using RNA molecules as templates. The generated protein

2378-460: The entire ribosome/mRNA complex binds to the outer membrane of the rough endoplasmic reticulum (ER), and the new protein is synthesized and released into the ER; the newly created polypeptide can be stored inside the ER for future vesicle transport and secretion outside the cell, or immediately secreted. Many types of transcribed RNA, such as tRNA, ribosomal RNA, and small nuclear RNA, do not undergo

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2436-486: The generated amino acid chain. The addition of an amino acid occurs at the C-terminus of the peptide; thus, translation is said to be amine-to-carboxyl directed. The mRNA carries genetic information encoded as a ribonucleotide sequence from the chromosomes to the ribosomes. The ribonucleotides are "read" by translational machinery in a sequence of nucleotide triplets called codons. Each of those triplets codes for

2494-480: The help of initiation factors (IF). In bacteria and a minority of archaea, initiation of protein synthesis involves the recognition of a purine-rich initiation sequence on the mRNA called the Shine–Dalgarno sequence . The Shine–Dalgarno sequence binds to a complementary pyrimidine-rich sequence on the 3' end of the 16S rRNA part of the 30S ribosomal subunit. The binding of these complementary sequences ensures that

2552-500: The host cell's ribosomes of its initial two large overlapping open reading frames (ORFs), 1a and 1b, both of which produce polyproteins . The functions of several of the viral proteins are known. ORFs 1a and 1b encode the replicase/transcriptase polyprotein, and later ORFs 2, 4, 5, and 9a encode, respectively, the four major structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N). The later ORFs also encode for eight unique proteins (orf3a to orf9b), known as

2610-420: The last four decades. Beyond chemical kinetics, various modeling formalisms such as Totally Asymmetric Simple Exclusion Process , Probabilistic Boolean Networks , Petri Nets and max-plus algebra have been applied to model the detailed kinetics of protein synthesis or some of its stages. A basic model of protein synthesis that takes into account all eight 'elementary' processes has been developed, following

2668-402: The mRNA, the three sites are oriented 5' to 3' E-P-A, because ribosomes move toward the 3' end of mRNA. The A-site binds the incoming tRNA with the complementary codon on the mRNA. The P/E-site holds the tRNA with the growing polypeptide chain. When an aminoacyl-tRNA initially binds to its corresponding codon on the mRNA, it is in the A site. Then, a peptide bond forms between the amino acid of

2726-421: The most basic "elementary" processes, consists of: The process of amino acid building to create protein in translation is a subject of various physic models for a long time starting from the first detailed kinetic models such as or others taking into account stochastic aspects of translation and using computer simulations. Many chemical kinetics-based models of protein synthesis have been developed and analyzed in

2784-460: The order of magnitude of 10 events per translated codon. The process of translation is highly regulated in both eukaryotic and prokaryotic organisms. Regulation of translation can impact the global rate of protein synthesis which is closely coupled to the metabolic and proliferative state of a cell. To delve deeper into this intricate process, scientists typically use a technique known as ribosome profiling. This method enables researchers to take

2842-424: The peptidyl transferase center of the ribosome. Drugs or special sequence motifs on the mRNA can change the ribosomal structure so that near-cognate tRNAs are bound to the stop codon instead of the release factors. In such cases of 'translational readthrough', translation continues until the ribosome encounters the next stop codon. Even though the ribosomes are usually considered accurate and processive machines,

2900-417: The polypeptide occurs when the A site of the ribosome is occupied by a stop codon (UAA, UAG, or UGA) on the mRNA, creating the primary structure of a protein. tRNA usually cannot recognize or bind to stop codons. Instead, the stop codon induces the binding of a release factor protein (RF1 & RF2) that prompts the disassembly of the entire ribosome/mRNA complex by the hydrolysis of the polypeptide chain from

2958-403: The process. After the new amino acid is added to the chain, and after the tRNA is released out of the ribosome and into the cytosol, the energy provided by the hydrolysis of a GTP bound to the translocase EF-G (in bacteria ) and a/eEF-2 (in eukaryotes and archaea ) moves the ribosome down one codon towards the 3' end . The energy required for translation of proteins is significant. For

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3016-406: The respective position in the protein. This "mistranslation" of the genetic code naturally occurs at low levels in most organisms, but certain cellular environments cause an increase in permissive mRNA decoding, sometimes to the benefit of the cell. The ribosome has two binding sites for tRNA. They are the aminoacyl site (abbreviated A), and the peptidyl site/ exit site (abbreviated P/E). Concerning

3074-404: The same cell in nature. These phenomena are known respectively as antigenic drift and antigenic shift . Microbial strains can also be differentiated by their genetic makeup using metagenomic methods to maximize resolution within species. This has become a valuable tool to analyze the microbiome . Scientists have modified strains of viruses in order to study their behavior, as in the case of

3132-467: The tRNA in the A site and the amino acid of the charged tRNA in the P/E site. The growing polypeptide chain is transferred to the tRNA in the A site. Translocation occurs, moving the tRNA to the P/E site, now without an amino acid; the tRNA that was in the A site, now charged with the polypeptide chain, is moved to the P/E site and the uncharged tRNA leaves, and another aminoacyl-tRNA enters the A site to repeat

3190-427: The term refers to the collective descendants produced from a common ancestor that share a uniform morphological or physiological character. A strain is a designated group of offspring that are either descended from a modified plant (produced by conventional breeding or by biotechnological means), or which result from genetic mutation. As an example, some rice strains are made by inserting new genetic material into

3248-540: The terms 'strain', ' variant ', and 'isolate' in the virology community, and most virologists simply copy the usage of terms from others". A strain is a genetic variant or subtype of a microorganism (e.g., a virus , bacterium or fungus ). For example, a "flu strain" is a certain biological form of the influenza or "flu" virus. These flu strains are characterized by their differing isoforms of surface proteins. New viral strains can be created due to mutation or swapping of genetic components when two or more viruses infect

3306-510: The translation process is subject to errors that can lead either to the synthesis of erroneous proteins or to the premature abandonment of translation, either because a tRNA couples to a wrong codon or because a tRNA is coupled to the wrong amino acid. The rate of error in synthesizing proteins has been estimated to be between 1 in 10 and 1 in 10 misincorporated amino acids, depending on the experimental conditions. The rate of premature translation abandonment, instead, has been estimated to be of

3364-407: The usual 5′ methylated cap and a 3′ polyadenylated tail . There are 265 nucleotides in the 5'UTR and 342 nucleotides in the 3'UTR . The 5' methylated cap and 3' polyadenylated tail allows the positive-sense RNA genome to be directly translated by the host cell's ribosome on viral entry . SARSr-CoV is similar to other coronaviruses in that its genome expression starts with translation by

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