Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs

Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs

N6-methyladenosine (m6A) is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m6A modifications to circular (circ) RNAs. We developed a computational pipeline (AutoCirc) that, together with depleti...

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Main Authors: Chan Zhou, Benoit Molinie, Kaveh Daneshvar, Joshua V. Pondick, Jinkai Wang, Nicholas Van Wittenberghe, Yi Xing, Cosmas C. Giallourakis, Alan C. Mullen
Format: Article
Language:English
Published: Elsevier 2017-08-01
Series:Cell Reports
Subjects:
circular RNAs
m6A modification
noncoding RNAs
embryonic stem cells
METTL3
YTHDF2
methyladenosine
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124717311348
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spelling doaj-15a0e1ac3f404bf389cf1dda227e5b5a2020-11-25T01:51:03ZengElsevierCell Reports2211-12472017-08-012092262227610.1016/j.celrep.2017.08.027Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAsChan Zhou0Benoit Molinie1Kaveh Daneshvar2Joshua V. Pondick3Jinkai Wang4Nicholas Van Wittenberghe5Yi Xing6Cosmas C. Giallourakis7Alan C. Mullen8Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USAGastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USAGastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USAGastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USADepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USAGastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USADepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USAGastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USAGastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USAN6-methyladenosine (m6A) is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m6A modifications to circular (circ) RNAs. We developed a computational pipeline (AutoCirc) that, together with depletion of ribosomal RNA and m6A immunoprecipitation, defined thousands of m6A circRNAs with cell-type-specific expression. The presence of m6A circRNAs is corroborated by interaction between circRNAs and YTHDF1/YTHDF2, proteins that read m6A sites in mRNAs, and by reduced m6A levels upon depletion of METTL3, the m6A writer. Despite sharing m6A readers and writers, m6A circRNAs are frequently derived from exons that are not methylated in mRNAs, whereas mRNAs that are methylated on the same exons that compose m6A circRNAs exhibit less stability in a process regulated by YTHDF2. These results expand our understanding of the breadth of m6A modifications and uncover regulation of circRNAs through m6A modification.http://www.sciencedirect.com/science/article/pii/S2211124717311348circular RNAsm6A modificationnoncoding RNAsembryonic stem cellsMETTL3YTHDF2methyladenosine
collection DOAJ
language English
format Article
sources DOAJ
author Chan Zhou
Benoit Molinie
Kaveh Daneshvar
Joshua V. Pondick
Jinkai Wang
Nicholas Van Wittenberghe
Yi Xing
Cosmas C. Giallourakis
Alan C. Mullen
spellingShingle Chan Zhou
Benoit Molinie
Kaveh Daneshvar
Joshua V. Pondick
Jinkai Wang
Nicholas Van Wittenberghe
Yi Xing
Cosmas C. Giallourakis
Alan C. Mullen
Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs
Cell Reports
circular RNAs
m6A modification
noncoding RNAs
embryonic stem cells
METTL3
YTHDF2
methyladenosine
author_facet Chan Zhou
Benoit Molinie
Kaveh Daneshvar
Joshua V. Pondick
Jinkai Wang
Nicholas Van Wittenberghe
Yi Xing
Cosmas C. Giallourakis
Alan C. Mullen
author_sort Chan Zhou
title Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs
title_short Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs
title_full Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs
title_fullStr Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs
title_full_unstemmed Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs
title_sort genome-wide maps of m6a circrnas identify widespread and cell-type-specific methylation patterns that are distinct from mrnas
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2017-08-01
description N6-methyladenosine (m6A) is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m6A modifications to circular (circ) RNAs. We developed a computational pipeline (AutoCirc) that, together with depletion of ribosomal RNA and m6A immunoprecipitation, defined thousands of m6A circRNAs with cell-type-specific expression. The presence of m6A circRNAs is corroborated by interaction between circRNAs and YTHDF1/YTHDF2, proteins that read m6A sites in mRNAs, and by reduced m6A levels upon depletion of METTL3, the m6A writer. Despite sharing m6A readers and writers, m6A circRNAs are frequently derived from exons that are not methylated in mRNAs, whereas mRNAs that are methylated on the same exons that compose m6A circRNAs exhibit less stability in a process regulated by YTHDF2. These results expand our understanding of the breadth of m6A modifications and uncover regulation of circRNAs through m6A modification.
topic circular RNAs
m6A modification
noncoding RNAs
embryonic stem cells
METTL3
YTHDF2
methyladenosine
url http://www.sciencedirect.com/science/article/pii/S2211124717311348
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