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Literature DB >> 31415754

Epitranscriptomic Addition of m⁵C to HIV-1 Transcripts Regulates Viral Gene Expression.

David G Courtney¹, Kevin Tsai¹, Hal P Bogerd¹, Edward M Kennedy¹, Brittany A Law², Ann Emery³, Ronald Swanstrom⁴, Christopher L Holley², Bryan R Cullen⁵.

Abstract

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.

Entities: CellLine Chemical Disease Gene Mutation Species

Keywords: 5-methyl cytosine; HIV-1; NSUN2; RNA modification; RNA splicing; epitranscriptomic; translation of mRNA

Mesh：

Substances：

Year: 2019 PMID： 31415754 PMCID： PMC6714563 DOI： 10.1016/j.chom.2019.07.005

Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023

51 in total

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Authors: Reuben S Harris; Kate N Bishop; Ann M Sheehy; Heather M Craig; Svend K Petersen-Mahrt; Ian N Watt; Michael S Neuberger; Michael H Malim
Journal: Cell Date: 2003-06-13 Impact factor: 41.582

2. Exposition of a family of RNA m(5)C methyltransferases from searching genomic and proteomic sequences.

Authors: R Reid; P J Greene; D V Santi
Journal: Nucleic Acids Res Date: 1999-08-01 Impact factor: 16.971

3. Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line.

Authors: J P Morgenstern; H Land
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4. Transcriptome-wide mapping of N(6)-methyladenosine by m(6)A-seq based on immunocapturing and massively parallel sequencing.

Authors: Dan Dominissini; Sharon Moshitch-Moshkovitz; Mali Salmon-Divon; Ninette Amariglio; Gideon Rechavi
Journal: Nat Protoc Date: 2013-01-03 Impact factor: 13.491

5. Human APOBEC3B is a potent inhibitor of HIV-1 infectivity and is resistant to HIV-1 Vif.

Authors: Brian P Doehle; Alexandra Schäfer; Bryan R Cullen
Journal: Virology Date: 2005-09-01 Impact factor: 3.616

6. RNA methyltransferases utilize two cysteine residues in the formation of 5-methylcytosine.

Authors: Michelle Y King; Kent L Redman
Journal: Biochemistry Date: 2002-09-17 Impact factor: 3.162

7. The Sequence Alignment/Map format and SAMtools.

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8. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.

Authors: Ben Langmead; Cole Trapnell; Mihai Pop; Steven L Salzberg
Journal: Genome Biol Date: 2009-03-04 Impact factor: 13.583

9. Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA.

Authors: Jeffrey E Squires; Hardip R Patel; Marco Nousch; Tennille Sibbritt; David T Humphreys; Brian J Parker; Catherine M Suter; Thomas Preiss
Journal: Nucleic Acids Res Date: 2012-02-16 Impact factor: 16.971

10. Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection.

Authors: Margherita Doria; Francesca Neri; Angela Gallo; Maria Giulia Farace; Alessandro Michienzi
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51 in total

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2. Mapping of pseudouridine residues on cellular and viral transcripts using a novel antibody-based technique.

Authors: Cecilia Martinez Campos; Kevin Tsai; David G Courtney; Hal P Bogerd; Christopher L Holley; Bryan R Cullen
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3. RNA bisulfite sequencing reveals NSUN2-mediated suppression of epithelial differentiation in pancreatic cancer.

Authors: Szu-Ying Chen; Kuan-Lin Chen; Li-Yun Ding; Chien-Hung Yu; Hsin-Yi Wu; Ya-Yi Chou; Chia-Jung Chang; Chih-Han Chang; Ya-Na Wu; Shang-Rung Wu; Ya-Chin Hou; Chung-Ta Lee; Peng-Chieh Chen; Yan-Shen Shan; Po-Hsien Huang
Journal: Oncogene Date: 2022-05-02 Impact factor: 9.867

Epitranscriptomic Addition of m⁵C to HIV-1 Transcripts Regulates Viral Gene Expression.

1. DNA deamination mediates innate immunity to retroviral infection.

2. Exposition of a family of RNA m(5)C methyltransferases from searching genomic and proteomic sequences.

3. Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line.

4. Transcriptome-wide mapping of N(6)-methyladenosine by m(6)A-seq based on immunocapturing and massively parallel sequencing.

5. Human APOBEC3B is a potent inhibitor of HIV-1 infectivity and is resistant to HIV-1 Vif.

6. RNA methyltransferases utilize two cysteine residues in the formation of 5-methylcytosine.

7. The Sequence Alignment/Map format and SAMtools.

8. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.

9. Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA.

10. Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection.

1. 5-Methylcytosine RNA Modifications Promote Retrovirus Replication in an ALYREF Reader Protein-Dependent Manner.

2. Mapping of pseudouridine residues on cellular and viral transcripts using a novel antibody-based technique.

3. RNA bisulfite sequencing reveals NSUN2-mediated suppression of epithelial differentiation in pancreatic cancer.

4. NSUN2-mediated RNA m⁵C modification modulates uveal melanoma cell proliferation and migration.

5. Unraveling the RNA modification code with mass spectrometry.

6. Acetylation of Cytidine Residues Boosts HIV-1 Gene Expression by Increasing Viral RNA Stability.

Review 7. HIV-1 Replication Benefits from the RNA Epitranscriptomic Code.

8. Mapping RNA Modifications Using Photo-Crosslinking-Assisted Modification Sequencing.

Review 9. An epigenetic 'extreme makeover': the methylation of flaviviral RNA (and beyond).

Review 10. RNA Methylation in Systemic Lupus Erythematosus.