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N 6 -methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression

Title: N 6 -methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression
Authors: Tirumuru, Nagaraja; Zhao, Boxuan Simen; Lu, Wuxun; Lu, Zhike; He, Chuan; Wu, Li
Source: http://knowledge.uchicago.edu/record/9991.
Publication Year: 2023
Collection: Knowledge@UChicago (University of Chicago)
Description: 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.
Document Type: text
Language: English
Relation: https://knowledge.uchicago.edu/record/9991/files/elife-15528-v4.pdf; http://knowledge.uchicago.edu/record/9991
DOI: 10.7554/eLife.15528
Availability: https://doi.org/10.7554/eLife.15528; http://knowledge.uchicago.edu/record/9991
Accession Number: edsbas.BB1DB0C3
Database: BASE