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RNA 3'-end mismatch excision by the severe acute respiratory syndrome coronavirus nonstructural protein nsp10/nsp14 exoribonuclease complex
- Source :
- Proceedings of the National Academy of Sciences; Vol 109, HEALTH FP7 Publications Database, PubMed Central, Proceedings of the National Academy of Sciences
- Publication Year :
- 2012
- Publisher :
- National Academy of Sciences, 2012.
-
Abstract
- The replication/transcription complex of severe acute respiratory syndrome coronavirus is composed of at least 16 nonstructural proteins (nsp1–16) encoded by the ORF-1a/1b. This complex includes replication enzymes commonly found in positive-strand RNA viruses, but also a set of RNA-processing activities unique to some nidoviruses. The nsp14 protein carries both exoribonuclease (ExoN) and (guanine-N7)-methyltransferase (N7-MTase) activities. The nsp14 ExoN activity ensures a yet-uncharacterized function in the virus life cycle and must be regulated to avoid nonspecific RNA degradation. In this work, we show that the association of nsp10 with nsp14 stimulates >35-fold the ExoN activity of the latter while playing no effect on N7-MTase activity. Nsp10 mutants unable to interact with nsp14 are not proficient for ExoN activation. The nsp10/nsp14 complex hydrolyzes double-stranded RNA in a 3′ to 5′ direction as well as a single mismatched nucleotide at the 3′-end mimicking an erroneous replication product. In contrast, di-, tri-, and longer unpaired ribonucleotide stretches, as well as 3′-modified RNAs, resist nsp10/nsp14-mediated excision. In addition to the activation of nsp16-mediated 2′-O-MTase activity, nsp10 also activates nsp14 in an RNA processing function potentially connected to a replicative mismatch repair mechanism.
- Subjects :
- 0303 health sciences
Multidisciplinary
Base Pair Mismatch
030302 biochemistry & molecular biology
RNA-dependent RNA polymerase
RNA
Biology
Biological Sciences
Viral Nonstructural Proteins
Molecular biology
3. Good health
03 medical and health sciences
Exon
RNA silencing
Open Reading Frames
Severe acute respiratory syndrome-related coronavirus
Exoribonuclease
Transcription preinitiation complex
Exoribonucleases
Exoribonuclease complex
RNA, Viral
DNA mismatch repair
RNA Processing, Post-Transcriptional
030304 developmental biology
Subjects
Details
- Language :
- English
- ISSN :
- 10916490
- Volume :
- 109
- Issue :
- 24
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....2d6a9e7729fd7b1da06e9a30ac1d1ae0
- Full Text :
- https://doi.org/10.1073/pnas.1201130109