Coronavirus 3′ UTR
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Coronavirus Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans and birds, they cause respiratory tract infections that can range from mild to lethal. Mild illnesses in humans include some cases of the comm ...
genomes are positive-sense single-stranded
RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
molecules with an
untranslated region In molecular genetics, an untranslated region (or UTR) refers to either of two sections, one on each side of a coding sequence on a strand of mRNA. If it is found on the Directionality (molecular biology), 5' side, it is called the Five prime ...
(UTR) at the
3′ end Directionality, in molecular biology and biochemistry, is the end-to-end chemical orientation of a single strand of nucleic acid. In a single strand of DNA or RNA, the chemical convention of naming carbon atoms in the nucleotide pentose-sugar-ri ...
which is called the
3′ UTR In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionally ...
. The 3′ UTR is responsible for important biological functions, such as viral replication. The 3′ UTR has a conserved RNA
secondary structure Protein secondary structure is the local spatial conformation of the polypeptide backbone excluding the side chains. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...
but different Coronavirus genera ( Alpha-, Beta-, Gamma-, and Deltacoronaviruses) have different structural features described below.


Alphacoronavirus 3′ UTR

The 3′ UTR of
Alphacoronavirus Alphacoronaviruses (Alpha-CoV) are members of the first of the four genera (''Alpha''-, '' Beta-'', '' Gamma-'', and '' Delta-'') of coronaviruses. They are positive-sense, single-stranded RNA viruses that infect mammals, including humans. They ...
es consists of two small hairpins (PK-SL2) which can form an alternate conformation (PK-SL1) where the loop region of the second hairpin interacts with the stem of the first hairpin (see
Coronavirus 3′ UTR pseudoknot The Coronavirus 3′ UTR pseudoknot is an RNA structure found in the coronavirus genome. Coronaviruses contain 30 kb single-stranded positive-sense RNA genomes. The 3′ UTR region of these coronavirus genomes contains a conserved ~55 nucleotide ...
). PK-SL2 has been confirmed in
HCoV-229E Human coronavirus 229E (HCoV-229E, ''Alphacoronavirus chicagoense'') is a species of coronavirus which infects humans and bats. It is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to the APN rec ...
and
HCoV-NL63 Human coronavirus NL63 (HCoV-NL63, ''Alphacoronavirus amsterdamense'') is a species of coronavirus, assigned to the subgenus '' Setracovirus'' and the genus ''Alphacoronavirus''. It was identified in late 2004 in patients in the Netherlands by Li ...
by in vitro structure probing experiments. Downstream of this pseudoknot lies the hypervariable region (HVR), which is supported by many covarying base pairs in alphacoronaviruses. Further, a conserved octanucleotide sequence 5′-GGAAGAGC-3′ is present in the HVR.


Betacoronavirus 3′ UTR

The 3′ UTR of
Betacoronavirus ''Betacoronavirus'' (β-CoVs or Beta-CoVs) is one of four genera (''Alphacoronavirus, Alpha''-, ''Beta-'', ''Gammacoronavirus, Gamma-'', and ''Deltacoronavirus (genus), Delta-'') of coronaviruses. Member viruses are Viral envelope, enveloped, p ...
es is approximately 300–500 nucleotides long. The most 5′ structure is the bulged stem-loop (BSL), starting downstream of the N gene
stop codon In molecular biology, a stop codon (or termination codon) is a codon (nucleotide triplet within messenger RNA) that signals the termination of the translation process of the current protein. Most codons in messenger RNA correspond to the additio ...
and is essential for viral replication. It is predicted to be conserved among Betacoronaviruses. Downstream to the BSL lies the hypervariable bulged-stemloop region (HVR), containing a triple helix junction. The hairpin stem-loop arising from this junction participates in the pseudoknot pairing with the BSL region. The pseudoknot and the BSL partially overlap and therefore cannot be formed at the same time. It is proposed that the BSL and pseudoknot act as a molecular switch that may regulate a transition during viral RNA synthesis. Part of the HVR is the octanucleotide sequence 5′-GGAAGAGC-3′ which is conserved among Alpha- and Betacoronaviruses. The 3′ UTR of
SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic. The virus previously had the Novel coronavirus, provisional nam ...
is similar to other Betacoronaviruses and is approximately 300–500 nucleotides long.


Gammacoronavirus 3′ UTR

In
Gammacoronavirus ''Gammacoronavirus'' (Gamma-CoV) is one of the four genera (''Alphacoronavirus, Alpha''-, ''Betacoronavirus, Beta-'', ''Gamma-'', and ''Deltacoronavirus (genus), Delta-'') of coronaviruses. It is in the subfamily ''Orthocoronavirinae'' of the fa ...
es a stem-loop located at the 3′ UTR is observed, which is vital for viral replication. Even though a nearby pseudoknot structure, which has been observed in other genera of coronaviruses, is present, its functional importance has not been established yet.


Deltacoronavirus 3′ UTR

There are two smaller hairpins and the hypervariable region (HVR) present in the 3′ UTR of
Deltacoronavirus ''Deltacoronavirus'' (Delta-CoV) is one of the four genera ('' Alpha-'', '' Beta-'', '' Gamma-'', and ''Delta-'') of coronaviruses. It is in the subfamily ''Orthocoronavirinae'' of the family ''Coronaviridae''. They are enveloped, positive-sense, ...
es. The pseudoknot structure which is typical for Alpha- and Betacoronaviruses has not been predicted in Deltacoronaviruses so far.


See also

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Coronavirus 5′ UTR Coronavirus genomes are Positive-sense single-stranded RNA virus, positive-sense single-stranded RNA molecules with an untranslated region (UTR) at the Directionality (molecular biology), 5′ end which is called the Five prime untranslated region ...
*
Coronavirus 3′ UTR pseudoknot The Coronavirus 3′ UTR pseudoknot is an RNA structure found in the coronavirus genome. Coronaviruses contain 30 kb single-stranded positive-sense RNA genomes. The 3′ UTR region of these coronavirus genomes contains a conserved ~55 nucleotide ...
*
Coronavirus 3′ stem-loop II-like motif (s2m) The Coronavirus 3′ stem-loop II-like motif (also known as s2m) is a secondary structure motif identified in the 3′ untranslated region (3′UTR) of astrovirus, coronavirus and equine rhinovirus genomes. Its function is unknown, but various ...
*
Coronavirus frameshifting stimulation element In molecular biology, the coronavirus frameshifting stimulation element is a conserved stem-loop of RNA found in coronaviruses that can promote ribosomal frameshifting. Such RNA molecules interact with a downstream region to form a pseudoknot s ...
*
Coronavirus packaging signal The Coronavirus packaging signal is a conserved cis-regulatory element found in Betacoronavirus (part of the Coronavirus subfamily of viruses). It has an important role in regulating the packaging of the viral genome into the capsid. As part of t ...


References

{{DEFAULTSORT:Coronavirus 3' UTR Cis-regulatory RNA elements