N6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression
The internal N6-methyladenosine (m6A) methylation of eukaryotic nuclear RNA controls post-transcriptional gene expression, which is regulated by methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers) in cells. The YTH domain family proteins (YTHDF1–3) bind to m6A-mo...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/15528 |
| _version_ | 1811200341470871552 |
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| author | Nagaraja Tirumuru Boxuan Simen Zhao Wuxun Lu Zhike Lu Chuan He Li Wu |
| author_facet | Nagaraja Tirumuru Boxuan Simen Zhao Wuxun Lu Zhike Lu Chuan He Li Wu |
| author_sort | Nagaraja Tirumuru |
| collection | DOAJ |
| description | The internal N6-methyladenosine (m6A) methylation of eukaryotic nuclear RNA controls post-transcriptional gene expression, which is regulated by methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers) in cells. The YTH domain family proteins (YTHDF1–3) bind to m6A-modified cellular RNAs and affect RNA metabolism and processing. Here, we show that YTHDF1–3 proteins recognize m6A-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 m6A writers decreased HIV-1 Gag protein expression in virus-producing cells, while silencing the m6A erasers increased Gag expression. Our findings suggest an important role of m6A modification of HIV-1 RNA in viral infection and HIV-1 protein synthesis. |
| first_indexed | 2024-04-12T02:03:16Z |
| format | Article |
| id | doaj.art-38e9dc88f0df4d63b77090738ee2271b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:03:16Z |
| publishDate | 2016-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-38e9dc88f0df4d63b77090738ee2271b2022-12-22T03:52:36ZengeLife Sciences Publications LtdeLife2050-084X2016-07-01510.7554/eLife.15528N6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expressionNagaraja Tirumuru0Boxuan Simen Zhao1Wuxun Lu2Zhike Lu3Chuan He4Li Wu5https://orcid.org/0000-0002-5468-2487Center for Retrovirus Research, The Ohio State University, Columbus, United States; Department of Veterinary Biosciences, The Ohio State University, Columbus, United StatesDepartment of Chemistry, The University of Chicago, Chicago, United States; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States; Institute for Biophysical Dynamics, The University of Chicago, Chicago, United States; Howard Hughes Medical Institute, The University of Chicago, Chicago, United StatesCenter for Retrovirus Research, The Ohio State University, Columbus, United States; Department of Veterinary Biosciences, The Ohio State University, Columbus, United StatesDepartment of Chemistry, The University of Chicago, Chicago, United States; Institute for Biophysical Dynamics, The University of Chicago, Chicago, United States; Howard Hughes Medical Institute, The University of Chicago, Chicago, United States; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United StatesDepartment of Chemistry, The University of Chicago, Chicago, United States; Institute for Biophysical Dynamics, The University of Chicago, Chicago, United States; Howard Hughes Medical Institute, The University of Chicago, Chicago, United States; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United StatesCenter for Retrovirus Research, The Ohio State University, Columbus, United States; Department of Veterinary Biosciences, The Ohio State University, Columbus, United States; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, United States; Comprehensive Cancer Center, The Ohio State University, Columbus, United StatesThe internal N6-methyladenosine (m6A) methylation of eukaryotic nuclear RNA controls post-transcriptional gene expression, which is regulated by methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers) in cells. The YTH domain family proteins (YTHDF1–3) bind to m6A-modified cellular RNAs and affect RNA metabolism and processing. Here, we show that YTHDF1–3 proteins recognize m6A-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 m6A writers decreased HIV-1 Gag protein expression in virus-producing cells, while silencing the m6A erasers increased Gag expression. Our findings suggest an important role of m6A modification of HIV-1 RNA in viral infection and HIV-1 protein synthesis.https://elifesciences.org/articles/15528HIV-1replicationRNA methylationN6-methyladenosineYTHDF proteins |
| spellingShingle | Nagaraja Tirumuru Boxuan Simen Zhao Wuxun Lu Zhike Lu Chuan He Li Wu N6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression eLife HIV-1 replication RNA methylation N6-methyladenosine YTHDF proteins |
| title | N6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression |
| title_full | N6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression |
| title_fullStr | N6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression |
| title_full_unstemmed | N6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression |
| title_short | N6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression |
| title_sort | n6 methyladenosine of hiv 1 rna regulates viral infection and hiv 1 gag protein expression |
| topic | HIV-1 replication RNA methylation N6-methyladenosine YTHDF proteins |
| url | https://elifesciences.org/articles/15528 |
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