5-Methylcytosine RNA Modifications Promote Retrovirus Replication in an ALYREF Reader Protein-Dependent Manner
| Autor: | Tao Pan, Zhen Cai, Matthew J. Eckwahl, Pooja Patel, Wen Zhang, Julia Michalkiewicz, Ruyi Xu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
RNA Stability
viruses Immunology Genome Viral Virus Replication Microbiology Genome Virus Mice 03 medical and health sciences 0302 clinical medicine Retrovirus Virology Murine leukemia virus Animals Humans RNA Messenger 030304 developmental biology 0303 health sciences Messenger RNA biology Nuclear Proteins RNA-Binding Proteins RNA Methyltransferases DNA Methylation biology.organism_classification Virus-Cell Interactions Cell biology Leukemia Virus Murine HEK293 Cells Retroviridae Viral replication 030220 oncology & carcinogenesis Insect Science 5-Methylcytosine NIH 3T3 Cells RNA Viral Transcriptome Transcription Factors |
| Zdroj: | J Virol |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.00544-20 |
| Popis: | RNA modifications play diverse roles in regulating RNA function, and viruses co-opt these pathways for their own benefit. While recent studies have highlighted the importance of N(6)-methyladenosine (m(6)A)—the most abundant mRNA modification—in regulating retrovirus replication, the identification and function of other RNA modifications in viral biology have been largely unexplored. Here, we characterized the RNA modifications present in a model retrovirus, murine leukemia virus (MLV), using mass spectrometry and sequencing. We found that 5-methylcytosine (m(5)C) is highly enriched in viral genomic RNA relative to uninfected cellular mRNAs, and we mapped at single-nucleotide resolution the m(5)C sites, which are located in multiple clusters throughout the MLV genome. Further, we showed that the m(5)C reader protein ALYREF plays an important role in regulating MLV replication. Together, our results provide a complete m(5)C profile in a virus and its function in a eukaryotic mRNA. IMPORTANCE Over 130 modifications have been identified in cellular RNAs, which play critical roles in many cellular processes, from modulating RNA stability to altering translation efficiency. One such modification, 5-methylcytosine, is relatively abundant in mammalian mRNAs, but its precise location and function are not well understood. In this study, we identified unexpectedly high levels of m(5)C in the murine leukemia virus RNA, precisely mapped its location, and showed that ALYREF, a reader protein that specifically recognizes m(5)C, regulates viral production. Together, our findings provide a high-resolution atlas of m(5)C in murine leukemia virus and reveal a functional role of m(5)C in viral replication. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|