HNRNPA2B1 Is a Mediator of m6A-Dependent Nuclear RNA Processing Events

被引：1329

作者：

Alarcon, Claudio R. ^{[1
]}

Goodarzi, Hani ^{[1
]}

Lee, Hyeseung ^{[1
]}

Liu, Xuhang ^{[1
]}

Tavazoie, Saeed ^{[2
,3
]}

Tavazoie, Sohail F. ^{[1
]}

机构：

[1] Rockefeller Univ, Lab Syst Canc Biol, New York, NY 10065 USA

[2] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA

[3] Columbia Univ, Dept Syst Biol, New York, NY 10032 USA

来源：

CELL | 2015年 / 162卷 / 06期

关键词：

MESSENGER-RNA; PRIMARY MICRORNAS; METHYLATION; REVEALS; N-6-METHYLADENOSINE; COMPLEX; M6A; N6-METHYLADENOSINE; IDENTIFICATION; SPECIFICITY;

D O I：

10.1016/j.cell.2015.08.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

N-6-methyladenosine (m(6)A) is the most abundant internal modification of messenger RNA. While the presence of m(6)A on transcripts can impact nuclear RNA fates, a reader of this mark that mediates processing of nuclear transcripts has not been identified. We find that the RNA-binding protein HNRNPA2B1 binds m(6)A-bearing RNAs in vivo and in vitro and its biochemical footprint matches the m(6)A consensus motif. HNRNPA2B1 directly binds a set of nuclear transcripts and elicits similar alternative splicing effects as the m(6)A writer METTL3. Moreover, HNRNPA2B1 binds to m(6)A marks in a subset of primary miRNA transcripts, interacts with the microRNA Microprocessor complex protein DGCR8, and promotes primary miRNA processing. Also, HNRNPA2B1 loss and METTL3 depletion cause similar processing defects for these pri-miRNA precursors. We propose HNRNPA2B1 to be a nuclear reader of the m(6)A mark and to mediate, in part, this mark's effects on primary microRNA processing and alternative splicing.

引用

页码：1299 / 1308

页数：10

共 45 条

[1] N6-methyladenosine marks primary microRNAs for processing [J].

Alarcon, Claudio R. ;

Lee, Hyeseung ;

Goodarzi, Hani ;

Halberg, Nils ;

Tavazoie, Sohail F. .

NATURE, 2015, 519 (7544) :482-+

[2] m6A RNA Modification Controls Cell Fate Transition in Mammalian Embryonic Stem Cells [J].

Batista, Pedro J. ;

Molinie, Benoit ;

Wang, Jinkai ;

Qu, Kun ;

Zhang, Jiajing ;

Li, Lingjie ;

Bouley, Donna M. ;

Lujan, Ernesto ;

Haddad, Bahareh ;

Daneshvar, Kaveh ;

Carter, Ava C. ;

Flynn, Ryan A. ;

Zhou, Chan ;

Lim, Kok-Seong ;

Dedon, Peter ;

Wernig, Marius ;

Mullen, Alan C. ;

Xing, Yi ;

Giallourakis, Cosmas C. ;

Chang, Howard Y. .

CELL STEM CELL, 2014, 15 (06) :707-719

[3] N-6-METHYLADENOSINE RESIDUES IN AN INTRON-SPECIFIC REGION OF PROLACTIN PRE-MESSENGER-RNA [J].

CARROLL, SM ;

NARAYAN, P ;

ROTTMAN, FM .

MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (09) :4456-4465

[4]

CSEPANY T, 1990, J BIOL CHEM, V265, P20117

[5] Processing of primary microRNAs by the Microprocessor complex [J].

Denli, AM ;

Tops, BBJ ;

Plasterk, RHA ;

Ketting, RF ;

Hannon, GJ .

NATURE, 2004, 432 (7014) :231-235

[6] In vivo genome-wide profiling of RNA secondary structure reveals novel regulatory features [J].

Ding, Yiliang ;

Tang, Yin ;

Kwok, Chun Kit ;

Zhang, Yu ;

Bevilacqua, Philip C. ;

Assmann, Sarah M. .

NATURE, 2014, 505 (7485) :696-+

[7] Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq [J].

Dominissini, Dan ;

Moshitch-Moshkovitz, Sharon ;

Schwartz, Schraga ;

Salmon-Divon, Mali ;

Ungar, Lior ;

Osenberg, Sivan ;

Cesarkas, Karen ;

Jacob-Hirsch, Jasmine ;

Amariglio, Ninette ;

Kupiec, Martin ;

Sorek, Rotem ;

Rechavi, Gideon .

NATURE, 2012, 485 (7397) :201-U84

[8] A universal framework for regulatory element discovery across all Genomes and data types [J].

Elemento, Olivier ;

Slonim, Noam ;

Tavazoie, Saeed .

MOLECULAR CELL, 2007, 28 (02) :337-350

[9] METHYLATIONS OF ADENOSINE RESIDUES (M6A) IN PRE-MESSENGER RNA ARE IMPORTANT FOR FORMATION OF LATE SIMIAN VIRUS-40 MESSENGER-RNAS [J].

FINKEL, D ;

GRONER, Y .

VIROLOGY, 1983, 131 (02) :409-425

[10] An integrated ChIP-seq analysis platform with customizable workflows [J].

Giannopoulou, Eugenia G. ;

Elemento, Olivier .

BMC BIOINFORMATICS, 2011, 12

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