@article{TEXTUAL, recid = {9991}, author = {Tirumuru, Nagaraja and Zhao, Boxuan Simen and Lu, Wuxun and Lu, Zhike and He, Chuan and Wu, Li}, title = {&lt;i&gt;N&lt;/i&gt;&lt;sup&gt;6&lt;/sup&gt;-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression}, journal = {eLife}, address = {2016-07-02}, number = {TEXTUAL}, abstract = {The internal <i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A) methylation of eukaryotic nuclear RNA controls post-transcriptional gene expression, which is regulated by methyltransferases (writers), demethylases (erasers), and m<sup>6</sup>A-binding proteins (readers) in cells. The YTH domain family proteins (YTHDF1-3) bind to m<sup>6</sup>A-modified cellular RNAs and affect RNA metabolism and processing. Here, we show that YTHDF1-3 proteins recognize m<sup>6</sup>A-modified HIV-1 RNA and inhibit HIV-1 infection in cell lines and primary CD4<sup>+</sup> 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<sup>6</sup>A writers decreased HIV-1 Gag protein expression in virus-producing cells, while silencing the m<sup>6</sup>A erasers increased Gag expression. Our findings suggest an important role of m<sup>6</sup>A modification of HIV-1 RNA in viral infection and HIV-1 protein synthesis.}, url = {http://knowledge.uchicago.edu/record/9991}, }