Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs
| Autor: | Jinkai Wang, Alan C. Mullen, Cosmas Giallourakis, Kaveh Daneshvar, Benoit Molinie, Chan Zhou, Yi Xing, Nicholas Van Wittenberghe, Joshua V. Pondick |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adenosine Immunoprecipitation RNA Stability Human Embryonic Stem Cells Cell type specific Biology Methylation Genome Article General Biochemistry Genetics and Molecular Biology m6A modification 03 medical and health sciences Exon Humans RNA Messenger noncoding RNAs lcsh:QH301-705.5 RNA metabolism Genetics Base Sequence Genome Human Computational Biology RNA-Binding Proteins Exons Methyltransferases RNA Circular embryonic stem cells Ribosomal RNA 030104 developmental biology Gene Expression Regulation methyladenosine lcsh:Biology (General) YTHDF2 Exoribonucleases DNA Transposable Elements RNA METTL3 Half-Life HeLa Cells circular RNAs |
| Zdroj: | Cell Reports, Vol 20, Iss 9, Pp 2262-2276 (2017) |
| ISSN: | 2211-1247 |
| Popis: | Summary N 6 -methyladenosine (m 6 A) is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m 6 A modifications to circular (circ) RNAs. We developed a computational pipeline (AutoCirc) that, together with depletion of ribosomal RNA and m 6 A immunoprecipitation, defined thousands of m 6 A circRNAs with cell-type-specific expression. The presence of m 6 A circRNAs is corroborated by interaction between circRNAs and YTHDF1/YTHDF2, proteins that read m 6 A sites in mRNAs, and by reduced m 6 A levels upon depletion of METTL3, the m 6 A writer. Despite sharing m 6 A readers and writers, m 6 A circRNAs are frequently derived from exons that are not methylated in mRNAs, whereas mRNAs that are methylated on the same exons that compose m 6 A circRNAs exhibit less stability in a process regulated by YTHDF2. These results expand our understanding of the breadth of m 6 A modifications and uncover regulation of circRNAs through m 6 A modification. |
| Databáze: | OpenAIRE |
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