Translation of Replicase and Assembly of the Replication Transcription Complex

Stable Identifier
R-HSA-9679504
Type
Pathway
Species
Homo sapiens
Related Species
Human SARS coronavirus
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After entry and uncoating, the SARS-CoV-1 genomic RNA serves as a transcript to allow cap dependent translation of ORF1a to produce polyprotein pp1a. A slippery sequence and an RNA pseudoknot near the end of ORF1a enable 25 - 30% of the ribosomes to undergo -1 frameshifting, to continue translation of ORF1b to produce a longer polyprotein pp1ab. The autoproteolytic cleavage of pp1a and pp1ab generates 15-16 nonstructural proteins (nsps) with various functions. The RNA dependent RNA polymerase (RdRP) activity is encoded in nsp12, and papain like protease (PLPro) and main protease (Mpro) activities are encoded in nsp3 and nsp5, respectively. nsp3, 4, and 6 induce rearrangement of the cellular membrane to form double membrane vesicles (DMVs) where the coronavirus replication transcription complex (RTC) is assembled and anchored.

Programmed ribosomal frameshifting (PRF) may be regulated by viral or host factors in addition to viral RNA secondary structures. For example, PRF in the related arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) is transactivated by the viral protein nsp1, which interacts with the PRF signal via a putative RNA binding motif. A host RNA-binding protein called annexin A2 (ANXA2) binds the pseudoknot structure in the IBV genome. Host factors in the early secretory pathway appear to be involved in DMV formation and RTC assembly: Golgi specific brefeldin A resistance guanine nucleotide exchange factor 1 (GBF1) and its effector ADP ribosylation factor 1 (ARF1) are both required for normal DMV formation and efficient RNA replication of mouse hepatitis virus (MHV), a prototypic betacoronavirus that infects mice (Fung & Liu 2019).

Literature References
PubMed ID Title Journal Year
31226023 Human Coronavirus: Host-Pathogen Interaction

Fung, TS, Liu, DX

Annu. Rev. Microbiol. 2019
Participants
Participant Of
Disease
Name Identifier Synonyms
severe acute respiratory syndrome 2945 SARS-CoV infection, SARS
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