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      • Record: found
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      Extensive translation of circular RNAs driven by N 6-methyladenosine

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          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 6-methyladenosine (m 6A), the most abundant base modification of RNA, promotes efficient initiation of protein translation from circRNAs in human cells. We discover that consensus m 6A motifs are enriched in circRNAs and a single m 6A site is sufficient to drive translation initiation. This m 6A-driven translation requires initiation factor eIF4G2 and m 6A 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 6A-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.

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          Large-scale analysis of the yeast proteome by multidimensional protein identification technology.

          Michael Washburn, Dirk Wolters, John R R Yates (2001)
          We describe a largely unbiased method for rapid and large-scale proteome analysis by multidimensional liquid chromatography, tandem mass spectrometry, and database searching by the SEQUEST algorithm, named multidimensional protein identification technology (MudPIT). MudPIT was applied to the proteome of the Saccharomyces cerevisiae strain BJ5460 grown to mid-log phase and yielded the largest proteome analysis to date. A total of 1,484 proteins were detected and identified. Categorization of these hits demonstrated the ability of this technology to detect and identify proteins rarely seen in proteome analysis, including low-abundance proteins like transcription factors and protein kinases. Furthermore, we identified 131 proteins with three or more predicted transmembrane domains, which allowed us to map the soluble domains of many of the integral membrane proteins. MudPIT is useful for proteome analysis and may be specifically applied to integral membrane proteins to obtain detailed biochemical information on this unwieldy class of proteins.
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            Cytoplasmic m6A reader YTHDF3 promotes mRNA translation

            Ang Li, Yu-Sheng Chen, Xiao-Li Ping … (2017)
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              Methylated nucleotides block 5' terminus of HeLa cell messenger RNA.

              C. Wei, A Gershowitz, B. Moss (1975)
              Polyadenylylated [poly(A)+] mRNA from HeLa cells that were labeled with [3H-methyl]-methionine and 14C-uridine was isolated by poly(U)-Sepharose chromatography. The presence of approximately two methyl groups per 1000 nucleotides of poly(A)+ RNA was calculated from the 3H/14C ratios and known degrees of methylation of 18S and 28S ribosomal RNAs. All four 2'-O-methylribonucleosides, but only two base-methylated derivatives, 7-methylguanosine (7MeG) and 6-methyladenosine (6MeA), were identified. 6MeA was the major component accounting for approximately 50% of the total methyl-labeled ribonucleosides. 7MeG, comprising about 10% of the total, was present exclusively at the 5' terminus of the poly(A)+ RNA and could be removed by periodate oxidation and beta elimination. Evidence for a 5' to 5' linkage of 7MeG to adjacent 2'-O-methylribonucleosides through at least two and probably three phosphates to give structures of the type 7MeG5'ppp5pNMep- and 7MeG5'ppp5'NMepNmep- was presented. The previous finding of similar sequences of methylated nucleotides in mRNA synthesized in vitro by enzymes associated with virus cores indicates that blocked 5' termini may be a characteristic feature of mRNAs that function in eucaryotic cells.
              Article 0 comments Cited 281 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cell Res
                Journal ID (iso-abbrev): Cell Res
                Title: Cell Research
                Publisher: Nature Publishing Group
                ISSN (Print): 1001-0602
                ISSN (Electronic): 1748-7838
                Publication date (Print): May 2017
                Publication date (Electronic): 10 March 2017
                Publication date PMC-release: 1 May 2017
                Volume: 27
                Issue: 5
                Pages: 626-641
                Affiliations
                [1 ]Institute of Biochemistry, College of Life Sciences, Zhejiang University at Zijingang, Zhejiang , Hangzhou, Zhejiang 310058, China
                [2 ]CAS Key Lab for Computational Biology, CAS Center for Excellence in Molecular Cell Science, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, China
                [3 ]Department of Integrative Biology and Physiology and the Molecular Biology Institute, UCLA , Los Angeles, CA 90095, USA
                [4 ]Department of Pharmacology, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599, USA
                [5 ]Synthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology , Shanghai, China
                [6 ]National Center for Protein Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, China
                [7 ]Shanghai Science Research Center, Chinese Academy of Sciences , Shanghai 201204, China
                [8 ]Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, China
                [9 ]Institute of Cancer Stem Cell, Dalian Medical University , Dalian, Liaoning 116044, China
                Author notes
                [✝]

                These three authors contributed equally to this work.

                Article
                Publisher Item ID: cr201731
                DOI: 10.1038/cr.2017.31
                PMC ID: 5520850
                PubMed ID: 28281539
                SO-VID: 7fd9b150-3731-4bf7-bc9f-9dc31fbce2b3
                Copyright © Copyright © 2017 The Author(s)
                License:

                This work is licensed under a Creative Commons Attribution 4.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                Date received : 13 January 2017
                Date revision received : 03 February 2017
                Date accepted : 19 February 2017
                Categories
                Subject: Original Article

                ScienceOpen disciplines: Cell biology
                Keywords: n6-methyladenosine,circular rna,cap-independent translation,eif4g2
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: n6-methyladenosine, circular rna, cap-independent translation, eif4g2

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