TY - JOUR
T1 - N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis
AU - Edupuganti, Raghu R.
AU - Geiger, Simon
AU - Lindeboom, Rik G.H.
AU - Shi, Hailing
AU - Hsu, Phillip J.
AU - Lu, Zhike
AU - Wang, Shuang Yin
AU - Baltissen, Marijke P.A.
AU - Jansen, Pascal W.T.C.
AU - Rossa, Martin
AU - Müller, Markus
AU - Stunnenberg, Hendrik G.
AU - He, Chuan
AU - Carell, Thomas
AU - Vermeulen, Michiel
N1 - Funding Information:
We thank members of the Vermeulen lab for fruitful discussions. Work in the Vermeulen lab is supported by the NWO Gravitation program Cancer Genomics Netherlands. Work in the He lab is supported by NHGRI, NIH (HG008688). C.H. is an Investigator of the Howard Hughes Medical Institute. Work in the Carell lab is supported by Deutsche Forschungsgemeinschaft (grants SFB749, SFB1032 and SPP1784) and Bundesministerium für Bildung und Forschung (EXC114).
PY - 2017/10/5
Y1 - 2017/10/5
N2 - RNA modifications are integral to the regulation of RNA metabolism. One abundant mRNA modification is N6-methyladenosine (m6A), which affects various aspects of RNA metabolism, including splicing, translation and degradation. Current knowledge about the proteins recruited to m6A to carry out these molecular processes is still limited. Here we describe comprehensive and systematic mass-spectrometry-based screening of m6A interactors in various cell types and sequence contexts. Among the main findings, we identified G3BP1 as a protein that is repelled by m6A and positively regulates mRNA stability in an m6A-regulated manner. Furthermore, we identified FMR1 as a sequence-context-dependent m6A reader, thus revealing a connection between an mRNA modification and an autism spectrum disorder. Collectively, our data represent a rich resource and shed further light on the complex interplay among m6A, m6A interactors and mRNA homeostasis.
AB - RNA modifications are integral to the regulation of RNA metabolism. One abundant mRNA modification is N6-methyladenosine (m6A), which affects various aspects of RNA metabolism, including splicing, translation and degradation. Current knowledge about the proteins recruited to m6A to carry out these molecular processes is still limited. Here we describe comprehensive and systematic mass-spectrometry-based screening of m6A interactors in various cell types and sequence contexts. Among the main findings, we identified G3BP1 as a protein that is repelled by m6A and positively regulates mRNA stability in an m6A-regulated manner. Furthermore, we identified FMR1 as a sequence-context-dependent m6A reader, thus revealing a connection between an mRNA modification and an autism spectrum disorder. Collectively, our data represent a rich resource and shed further light on the complex interplay among m6A, m6A interactors and mRNA homeostasis.
UR - http://www.scopus.com/inward/record.url?scp=85030784919&partnerID=8YFLogxK
U2 - 10.1038/nsmb.3462
DO - 10.1038/nsmb.3462
M3 - Article
C2 - 28869609
AN - SCOPUS:85030784919
SN - 1545-9993
VL - 24
SP - 870
EP - 878
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 10
ER -