Polypeptide encoded by the -1 PRF signal of SARS-CoV-2 controls multiple enzymatic activities of the viral NiRAN domain.

ABSTRACT: The Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain is located amino-terminally to the RNA-dependent RNA polymerase (RdRp) in nonstructural protein (nsp)12 of SARS-CoV-2. The GDP-polyribonucleotidyltransferase (GDP-PRNT) and UMPylation activities of NiRAN contribute to viral RNA biogenesis by forming an RNA capping precursor and an RNA synthesis initiation primer, respectively. Translation of nsp12 is mediated by -1 programmed ribosomal frameshifting (-1 PRF), via an RNA signal composed of a slippery sequence and a downstream stimulator structure. The -1 PRF signal encodes a polypeptide, yet its function remains unexplored. Here, we show that the -1 PRF signal-encoded polypeptide is required for NiRAN activity. Mutational analysis reveals that a phenylalanine encoded by pa

SUBMITTER: Hsu HT 

PROVIDER: S-EPMC12628317 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature