Abstract
Most eukaryotic viruses that replicate in the cytoplasm, including coronaviruses, have evolved strategies to cap their RNAs. In our previous work, the nonstructural protein (nsp) 14 of severe acute respiratory syndrome coronavirus (SARS-CoV) was identified as a cap (guanine-N7)-methyltransferase (N7-MTase). In this study, we found that GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG could be methylated by SARS-CoV nsp14. In contrast, the nsp14 could not modify ATP, CTP, UTP, dATP, dCTP, dUTP or cap analog m7GpppA. Critical residues of nsp14 essential for the methyltransferase activity on GTP were identified, which include F73, R84, W86, R310, D331, G333, P335, Y368, C414, and C416. We further showed that the methyltransferase activity of GTP was universal for nsp14 of other coronaviruses. Moreover, the accumulation of m7GTP or presence of protein nsp14 could interfere with protein translation of cellular mRNAs. Altogether, the results revealed a new enzymatic activity of coronavirus nsp14.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 45-52 |
| Number of pages | 8 |
| Journal | Virus Research |
| Volume | 176 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Sep 2013 |
Funding
We thank Dr. J. Snijder for kindly providing SARS-CoV nsp12 expression plasmid. We are grateful to Dr. L. Enjuanes for providing TGEV cDNA. This study was supported by China Basic Research Program ( #2010CB911800 and 2013CB911101 ) and China NSFC grants ( #81130083 , #31170152 , #30925003 , #31000085 and #31221061 ).
Keywords
- Coronavirus
- GTP methylation
- Nsp14
- SARS
- Translation
ASJC Scopus subject areas
- Virology
- Infectious Diseases
- Cancer Research
