Journal article
N6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression
eLife, Vol.5(2016), e15528
07/02/2016
DOI: 10.7554/eLife.15528
PMCID: PMC4961459
PMID: 27371828
Abstract
The internal N-6-methyladenosine (m(6)A) methylation of eukaryotic nuclear RNA controls post-transcriptional gene expression, which is regulated by methyltransferases (writers), demethylases (erasers), and m(6)A-binding proteins (readers) in cells. The YTH domain family proteins (YTHDF1-3) bind to m(6)A-modified cellular RNAs and affect RNA metabolism and processing. Here, we show that YTHDF1-3 proteins recognize m(6)A-modified HIV-1 RNA and inhibit HIV-1 infection in cell lines and primary CD4(+) T-cells. We further mapped the YTHDF1-3 binding sites in HIV-1 RNA from infected cells. We found that the overexpression of YTHDF proteins in cells inhibited HIV-1 infection mainly by decreasing HIV-1 reverse transcription, while knockdown of YTHDF1-3 in cells had the opposite effects. Moreover, silencing the m(6)A writers decreased HIV-1 Gag protein expression in virus-producing cells, while silencing the m(6)A erasers increased Gag expression. Our findings suggest an important role of m(6)A modification of HIV-1 RNA in viral infection and HIV-1 protein synthesis.
Details
- Title: Subtitle
- N6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression
- Creators
- Nagaraja Tirumuru - The Ohio State UniversityBoxuan Simen Zhao - Howard Hughes Medical Institute, The University of ChicagoWuxun Lu - The Ohio State UniversityZhike Lu - Howard Hughes Medical Institute, The University of ChicagoChuan He - Howard Hughes Medical Institute, The University of ChicagoLi Wu - The Ohio State University
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.5(2016), e15528
- DOI
- 10.7554/eLife.15528
- PMID
- 27371828
- PMCID
- PMC4961459
- NLM abbreviation
- Elife
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Publisher
- eLife Sciences Publications, Ltd
- Grant note
- ; AI104483 / ; AI074658 / ; AI120209 / ; CA181997 / ; Seed Grant / ;
- Language
- English
- Date published
- 07/02/2016
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984001128402771
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