Extensive translation of circular RNAs driven by N 6 -methyladenosine
Extensive pre-mRNA back-splicing generates numerous circular RNAs (circRNAs) in human transcriptome. However, the biological functions of these circRNAs remain largely unclear. Here we report that N -methyladenosine (m A), the most abundant base modification of RNA, promotes efficient initiation of...
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| Veröffentlicht in: | Cell research 2017-05, Vol.27 (5), p.626 |
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| container_title | Cell research |
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| creator | Yang, Yun Fan, Xiaojuan Mao, Miaowei Song, Xiaowei Wu, Ping Zhang, Yang Jin, Yongfeng Yang, Yi Chen, Ling-Ling Wang, Yang Wong, Catherine Cl Xiao, Xinshu Wang, Zefeng |
| description | Extensive pre-mRNA back-splicing generates numerous circular RNAs (circRNAs) in human transcriptome. However, the biological functions of these circRNAs remain largely unclear. Here we report that N
-methyladenosine (m
A), the most abundant base modification of RNA, promotes efficient initiation of protein translation from circRNAs in human cells. We discover that consensus m
A motifs are enriched in circRNAs and a single m
A site is sufficient to drive translation initiation. This m
A-driven translation requires initiation factor eIF4G2 and m
A reader YTHDF3, and is enhanced by methyltransferase METTL3/14, inhibited by demethylase FTO, and upregulated upon heat shock. Further analyses through polysome profiling, computational prediction and mass spectrometry reveal that m
A-driven translation of circRNAs is widespread, with hundreds of endogenous circRNAs having translation potential. Our study expands the coding landscape of human transcriptome, and suggests a role of circRNA-derived proteins in cellular responses to environmental stress. |
| doi_str_mv | 10.1038/cr.2017.31 |
| format | Article |
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-methyladenosine (m
A), the most abundant base modification of RNA, promotes efficient initiation of protein translation from circRNAs in human cells. We discover that consensus m
A motifs are enriched in circRNAs and a single m
A site is sufficient to drive translation initiation. This m
A-driven translation requires initiation factor eIF4G2 and m
A reader YTHDF3, and is enhanced by methyltransferase METTL3/14, inhibited by demethylase FTO, and upregulated upon heat shock. Further analyses through polysome profiling, computational prediction and mass spectrometry reveal that m
A-driven translation of circRNAs is widespread, with hundreds of endogenous circRNAs having translation potential. Our study expands the coding landscape of human transcriptome, and suggests a role of circRNA-derived proteins in cellular responses to environmental stress.</description><identifier>EISSN: 1748-7838</identifier><identifier>DOI: 10.1038/cr.2017.31</identifier><identifier>PMID: 28281539</identifier><language>eng</language><publisher>England</publisher><subject>Adenosine - analogs & derivatives ; Adenosine - metabolism ; Eukaryotic Initiation Factor-3 - metabolism ; Eukaryotic Initiation Factor-4G - metabolism ; HeLa Cells ; Humans ; Nucleotide Motifs - genetics ; Peptides - chemistry ; Peptides - metabolism ; Protein Biosynthesis ; RNA - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Tandem Mass Spectrometry ; Transcriptome - genetics</subject><ispartof>Cell research, 2017-05, Vol.27 (5), p.626</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28281539$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Yun</creatorcontrib><creatorcontrib>Fan, Xiaojuan</creatorcontrib><creatorcontrib>Mao, Miaowei</creatorcontrib><creatorcontrib>Song, Xiaowei</creatorcontrib><creatorcontrib>Wu, Ping</creatorcontrib><creatorcontrib>Zhang, Yang</creatorcontrib><creatorcontrib>Jin, Yongfeng</creatorcontrib><creatorcontrib>Yang, Yi</creatorcontrib><creatorcontrib>Chen, Ling-Ling</creatorcontrib><creatorcontrib>Wang, Yang</creatorcontrib><creatorcontrib>Wong, Catherine Cl</creatorcontrib><creatorcontrib>Xiao, Xinshu</creatorcontrib><creatorcontrib>Wang, Zefeng</creatorcontrib><title>Extensive translation of circular RNAs driven by N 6 -methyladenosine</title><title>Cell research</title><addtitle>Cell Res</addtitle><description>Extensive pre-mRNA back-splicing generates numerous circular RNAs (circRNAs) in human transcriptome. However, the biological functions of these circRNAs remain largely unclear. Here we report that N
-methyladenosine (m
A), the most abundant base modification of RNA, promotes efficient initiation of protein translation from circRNAs in human cells. We discover that consensus m
A motifs are enriched in circRNAs and a single m
A site is sufficient to drive translation initiation. This m
A-driven translation requires initiation factor eIF4G2 and m
A reader YTHDF3, and is enhanced by methyltransferase METTL3/14, inhibited by demethylase FTO, and upregulated upon heat shock. Further analyses through polysome profiling, computational prediction and mass spectrometry reveal that m
A-driven translation of circRNAs is widespread, with hundreds of endogenous circRNAs having translation potential. Our study expands the coding landscape of human transcriptome, and suggests a role of circRNA-derived proteins in cellular responses to environmental stress.</description><subject>Adenosine - analogs & derivatives</subject><subject>Adenosine - metabolism</subject><subject>Eukaryotic Initiation Factor-3 - metabolism</subject><subject>Eukaryotic Initiation Factor-4G - metabolism</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Nucleotide Motifs - genetics</subject><subject>Peptides - chemistry</subject><subject>Peptides - metabolism</subject><subject>Protein Biosynthesis</subject><subject>RNA - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Tandem Mass Spectrometry</subject><subject>Transcriptome - genetics</subject><issn>1748-7838</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1j11LwzAYRoMgbk5v_AGSP9Caj6ZJLseoThgTxrwe-XiDlTYtSSf23ztQr56bw-E8CD1QUlLC1ZNLJSNUlpxeoSWVlSqk4mqBbnP-JISJStAbtGCKKSq4XqKm-Z4g5vYL8JRMzJ2Z2iHiIWDXJnfuTMKH_Tpjny5IxHbGe1zjoofpY-6MhzjkNsIdug6my3D_tyv0_twcN9ti9_byulnvipFKNRVGQ21BOcuoE5XTlQUXODeECC6CZt5byYATUevgwyXVSCaBO1sRKqwGvkKPv97xbHvwpzG1vUnz6f8P_wH4fkov</recordid><startdate>201705</startdate><enddate>201705</enddate><creator>Yang, Yun</creator><creator>Fan, Xiaojuan</creator><creator>Mao, Miaowei</creator><creator>Song, Xiaowei</creator><creator>Wu, Ping</creator><creator>Zhang, Yang</creator><creator>Jin, Yongfeng</creator><creator>Yang, Yi</creator><creator>Chen, Ling-Ling</creator><creator>Wang, Yang</creator><creator>Wong, Catherine Cl</creator><creator>Xiao, Xinshu</creator><creator>Wang, Zefeng</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>201705</creationdate><title>Extensive translation of circular RNAs driven by N 6 -methyladenosine</title><author>Yang, Yun ; Fan, Xiaojuan ; Mao, Miaowei ; Song, Xiaowei ; Wu, Ping ; Zhang, Yang ; Jin, Yongfeng ; Yang, Yi ; Chen, Ling-Ling ; Wang, Yang ; Wong, Catherine Cl ; Xiao, Xinshu ; Wang, Zefeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p178t-a9e6be8cb21c54c94becf33a00535f92ddb72e30569fdf451a727e3cb4015b9e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adenosine - analogs & derivatives</topic><topic>Adenosine - metabolism</topic><topic>Eukaryotic Initiation Factor-3 - metabolism</topic><topic>Eukaryotic Initiation Factor-4G - metabolism</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Nucleotide Motifs - genetics</topic><topic>Peptides - chemistry</topic><topic>Peptides - metabolism</topic><topic>Protein Biosynthesis</topic><topic>RNA - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Tandem Mass Spectrometry</topic><topic>Transcriptome - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Yun</creatorcontrib><creatorcontrib>Fan, Xiaojuan</creatorcontrib><creatorcontrib>Mao, Miaowei</creatorcontrib><creatorcontrib>Song, Xiaowei</creatorcontrib><creatorcontrib>Wu, Ping</creatorcontrib><creatorcontrib>Zhang, Yang</creatorcontrib><creatorcontrib>Jin, Yongfeng</creatorcontrib><creatorcontrib>Yang, Yi</creatorcontrib><creatorcontrib>Chen, Ling-Ling</creatorcontrib><creatorcontrib>Wang, Yang</creatorcontrib><creatorcontrib>Wong, Catherine Cl</creatorcontrib><creatorcontrib>Xiao, Xinshu</creatorcontrib><creatorcontrib>Wang, Zefeng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Cell research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Yun</au><au>Fan, Xiaojuan</au><au>Mao, Miaowei</au><au>Song, Xiaowei</au><au>Wu, Ping</au><au>Zhang, Yang</au><au>Jin, Yongfeng</au><au>Yang, Yi</au><au>Chen, Ling-Ling</au><au>Wang, Yang</au><au>Wong, Catherine Cl</au><au>Xiao, Xinshu</au><au>Wang, Zefeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extensive translation of circular RNAs driven by N 6 -methyladenosine</atitle><jtitle>Cell research</jtitle><addtitle>Cell Res</addtitle><date>2017-05</date><risdate>2017</risdate><volume>27</volume><issue>5</issue><spage>626</spage><pages>626-</pages><eissn>1748-7838</eissn><abstract>Extensive pre-mRNA back-splicing generates numerous circular RNAs (circRNAs) in human transcriptome. However, the biological functions of these circRNAs remain largely unclear. Here we report that N
-methyladenosine (m
A), the most abundant base modification of RNA, promotes efficient initiation of protein translation from circRNAs in human cells. We discover that consensus m
A motifs are enriched in circRNAs and a single m
A site is sufficient to drive translation initiation. This m
A-driven translation requires initiation factor eIF4G2 and m
A reader YTHDF3, and is enhanced by methyltransferase METTL3/14, inhibited by demethylase FTO, and upregulated upon heat shock. Further analyses through polysome profiling, computational prediction and mass spectrometry reveal that m
A-driven translation of circRNAs is widespread, with hundreds of endogenous circRNAs having translation potential. Our study expands the coding landscape of human transcriptome, and suggests a role of circRNA-derived proteins in cellular responses to environmental stress.</abstract><cop>England</cop><pmid>28281539</pmid><doi>10.1038/cr.2017.31</doi><oa>free_for_read</oa></addata></record> |
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| identifier | EISSN: 1748-7838 |
| ispartof | Cell research, 2017-05, Vol.27 (5), p.626 |
| issn | 1748-7838 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SpringerLink Journals - AutoHoldings |
| subjects | Adenosine - analogs & derivatives Adenosine - metabolism Eukaryotic Initiation Factor-3 - metabolism Eukaryotic Initiation Factor-4G - metabolism HeLa Cells Humans Nucleotide Motifs - genetics Peptides - chemistry Peptides - metabolism Protein Biosynthesis RNA - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Tandem Mass Spectrometry Transcriptome - genetics |
| title | Extensive translation of circular RNAs driven by N 6 -methyladenosine |
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