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 com ...
genomes are
positive-sense single-stranded RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
molecules with an
untranslated region (UTR) at the
5′ 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- ...
which is called the
5′ UTR
The 5′ untranslated region (also known as 5′ UTR, leader sequence, transcript leader, or leader RNA) is the region of a messenger RNA (mRNA) that is directly upstream from the initiation codon. This region is important for the regulation of ...
. The 5′ UTR is responsible for important biological functions, such as viral
replication,
transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
and packaging.
The 5′ UTR has a conserved RNA
secondary structure
Protein secondary structure is the three dimensional conformational isomerism, form of ''local segments'' of proteins. 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 5′ UTR

The first 150 to 200
nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
s within the 5′ UTR of
Alphacoronaviruses are highly structured and shown to be
conserved on the structural level. The 5′ UTRs are predicted to contain three conserved
stem-loop
Stem-loop intramolecular base pairing is a pattern that can occur in single-stranded RNA. The structure is also known as a hairpin or hairpin loop. It occurs when two regions of the same strand, usually complementary in nucleotide sequence when ...
s:
* SL1 is important for viral replication, most likely playing a role in the template-switch of viral
subgenomic RNA
Subgenomic mRNAs are essentially smaller sections of the original transcribed template strand.
3' to 5' DNA or RNA
During transcription, the original template strand is usually read from the 3' to the 5' end from beginning to end. Subgenomic m ...
(sgRNA)
transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
.
Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s of the upper part of SL1 seem to have a higher impact of viral replication level.
* SL2 is crucial for viral viability. Nucleotides are interchangeable as long as the structure remains stable. Disrupting any G-C pairing causes major defects in viral replication.
* SL4 is hypothesised to play a role in directing subgenomic RNA synthesis during viral replication.
Downstream of SL4 lies SL5, which overlaps with the first
ORF
ORF or Orf may refer to:
* Norfolk International Airport, IATA airport code ORF
* Observer Research Foundation, an Indian research institute
* One Race Films, a film production company founded by Vin Diesel
* Open reading frame, a portion of the ...
of the viral genome. The three terminal loops of SL5 contain a conserved sequence
5′-UUCCGU-3′
and are thought to act as the packaging signal.
Betacoronavirus 5′ UTR

Similar to Alphacoronavirus, the first 150 to 200 nucleotides within the
Betacoronavirus 5′ UTR are highly structured and contains three conserved stem-loops (SL1, SL2 and SL4).
SARS-CoV
Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; or Severe acute respiratory syndrome coronavirus, SARS-CoV) is a strain of coronavirus that causes severe acute respiratory syndrome (SARS), the respiratory illness responsible for t ...
and
BCoV have an additional stem-loop, called SL3, which contains the TRS-L sequence in its loop region. This is crucial for sgRNA synthesis during viral replication. However, according to predictions, SL3 is not stable in other Betacoronaviruses like
MHV.
Similar to other Sarbecoviruses, the 5′ UTR of
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...
is predicted to consist of 4 distinct stem-loops, namely SL1, SL2, SL3 and SL4. Further, there is a larger structure, SL5, present, which includes the first ORFs of the
polyprotein pp1a. Note, that SL3 is typically present in SARS coronaviruses, but not necessarily conserved among other Betacoronaviruses.
Gammacoronavirus 5′ UTR
The 5′ UTR of
Gammacoronavirus
''Gammacoronavirus'' (Gamma-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 is similar to the 5′ UTRs of Alpha- and Betacoronaviruses, as they also contain three helices denoted as SL1, SL2 and SL4. Further, in a subset of Gammacoronaviruses a third stem-loop, SL3, is observed. SL1 and SL2 have major impacts of the level of viral replication, whereas SL4 is hypothesized to play a role as a "spacer" during the template-switch of sgRNA synthesis.
Deltacoronavirus 5′ UTR

The 5′UTR of
Deltacoronaviruses is similar to the 5′UTRs of Alpha- and Betacoronaviruses, as they also contain three helices denoted as SL1, SL2 and SL4. Predictions show a conserved fourth stem-loop (SL3) between SL2 and SL4, sometimes observed in Beta- and Gammacoronaviruses as well. SL3 usually exposes the TRS-L sequence in the loop region.
See also
*
Coronavirus 3′ UTR
Coronavirus genomes are positive-sense single-stranded RNA molecules with an untranslated region (UTR) at the 3′ end which is called the 3′ UTR. The 3′ UTR is responsible for important biological functions, such as viral replication. The 3 ...
*
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′ UTR, 3′ untranslated region (3′UTR) of astrovirus, coronavirus and equine rhinovirus genomes. Its function is unknown, but ...
*
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 str ...
*
Coronavirus packaging signal
References
{{DEFAULTSORT:Coronavirus 5' UTR
Cis-regulatory RNA elements