The Coronavirus packaging signal is a conserved
cis-regulatory element found in
Betacoronavirus (part of the
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 ...
subfamily of
viruses
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
). It has an important role in regulating the packaging of the viral
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
into the
capsid. As part of the viral life cycle, within the infected cell, the viral genome becomes associated with viral
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s and assembles into new infective
progeny viruses. This process is called packaging and is vital for viral replication.
The packaging signal is found in the
positive-sense
In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context, ...
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 ...
genome. It interacts with the viral proteins (
M and
N)
and ensures the selective packaging of viral RNA into
virions.
This RNA element is conserved in
Embecovirus (previously known as lineage A Betacoronavirus), which includes
mouse hepatitis virus
Murine coronavirus (M-CoV) is a virus in the genus ''Betacoronavirus'' that infects mice. Belonging to the subgenus ''Embecovirus'', murine coronavirus strains are enterotropic or polytropic. Enterotropic strains include mouse hepatitis virus (M ...
(MHV),
bovine coronavirus
Bovine coronavirus (BCV or BCoV) is a coronavirus which is a member of the species ''Betacoronavirus 1''. The infecting virus is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to the N-acetyl-9-O ...
(BCoV), and human coronaviruses like
HCoV-HKU1
''Human coronavirus HKU1'' (''HCoV-HKU1'') is a species of coronavirus in humans and animals. It causes an upper respiratory disease with symptoms of the common cold, but can advance to pneumonia and bronchiolitis. It was first discovered in Janu ...
and
HCoV-OC43
Human coronavirus OC43 (HCoV-OC43) is a member of the species ''Betacoronavirus 1'', which infects humans and cattle. The infecting coronavirus is an enveloped, positive-sense, single-stranded RNA virus that enters its host cell by binding to th ...
. Notably, this element is absent from the other viral lineages which have evolved separate packaging signals. For example, it is not found in
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
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 ...
(contrary to previous claims that have been refuted).
The packaging signal has a conserved
RNA secondary structure
Nucleic acid secondary structure is the basepairing interactions within a single nucleic acid polymer or between two polymers. It can be represented as a list of bases which are paired in a nucleic acid molecule.
The secondary structures of biolo ...
featuring four AGC/GUAAU internal loop motifs. Within the viral genome the packaging signal is located in the
nonstructural protein In virology, a nonstructural protein is a protein encoded by a virus but that is not part of the viral particle. They typically include the various enzymes and transcription factors the virus uses to replicate itself, such as a viral protease ( 3CL ...
15 (nsp15) and encodes a
polypeptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
which is found on the surface of the nsp15 protein. Deleting the packaging signal or introducing mutations that disrupt its secondary structure but not the encoded peptide lead to the loss of packaging specificity. At the same time, relocating the packaging signal to a different part of the genome did not have a negative effect on packaging.
Other RNA families identified in the coronavirus include the
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 ...
, the
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 ...
, as well as the 5′- and
3′ UTR pseudoknot.
See also
*
Coronavirus 5′ UTR
Coronavirus genomes are positive-sense single-stranded RNA molecules with an untranslated region (UTR) at the 5′ end which is called the 5′ UTR. The 5′ UTR is responsible for important biological functions, such as viral replication, tran ...
*
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 ...
References
External links
*
Cis-regulatory RNA elements
Coronaviridae
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