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Epitranscriptomic Addition of m5C to HIV-1 Transcripts Regulates Viral Gene Expression
- Source :
- Cell Host & Microbe
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Summary How the covalent modification of mRNA ribonucleotides, termed epitranscriptomic modifications, alters mRNA function remains unclear. One issue has been the difficulty of quantifying these modifications. Using purified HIV-1 genomic RNA, we show that this RNA bears more epitranscriptomic modifications than the average cellular mRNA, with 5-methylcytosine (m5C) and 2′O-methyl modifications being particularly prevalent. The methyltransferase NSUN2 serves as the primary writer for m5C on HIV-1 RNAs. NSUN2 inactivation inhibits not only m5C addition to HIV-1 transcripts but also viral replication. This inhibition results from reduced HIV-1 protein, but not mRNA, expression, which in turn correlates with reduced ribosome binding to viral mRNAs. In addition, loss of m5C dysregulates the alternative splicing of viral RNAs. These data identify m5C as a post-transcriptional regulator of both splicing and function of HIV-1 mRNA, thereby affecting directly viral gene expression.
- Subjects :
- 0303 health sciences
Messenger RNA
Methyltransferase
Alternative splicing
Regulator
RNA
Biology
Microbiology
Ribosome
3. Good health
Cell biology
03 medical and health sciences
0302 clinical medicine
Viral replication
Virology
RNA splicing
Parasitology
030217 neurology & neurosurgery
030304 developmental biology
Subjects
Details
- ISSN :
- 19313128
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Cell Host & Microbe
- Accession number :
- edsair.doi.dedup.....64ff997bfbe416c42cb0539da08674b8