NSUN2‐Mediated m5C Methylation and METTL3/METTL14‐Mediated m6A Methylation Cooperatively Enhance p21 Translation

ABSTRACT N6‐methyladenosine (m6A) and m5C methylation are two major types of RNA methylation, but the impact of joint modifications on the same mRNA is unknown. Here, we show that in p21 3′UTR, NSUN2 catalyzes m5C modification and METTL3/METTL14 catalyzes m6A modification. Interestingly, methylation...

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Published in:Journal of cellular biochemistry Vol. 118; no. 9; pp. 2587 - 2598
Main Authors: Li, Qiu, Li, Xiu, Tang, Hao, Jiang, Bin, Dou, Yali, Gorospe, Myriam, Wang, Wengong
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 01.09.2017
Subjects:
3' Untranslated Regions
Adenosine - analogs & derivatives
Adenosine - genetics
Adenosine - metabolism
Biochemistry
Cellular Senescence - genetics
Cyclin-Dependent Kinase Inhibitor p21 - biosynthesis
Cyclin-Dependent Kinase Inhibitor p21 - genetics
Gene expression
Gene Expression Regulation
GTP-binding protein
HeLa Cells
Humans
Methylation
Methyltransferases - genetics
Methyltransferases - metabolism
METTL14
METTL3
N6-methyladenosine
NSUN2
Oxidative stress
Oxidative Stress - genetics
p21 mRNA METHYLATION
Protein Biosynthesis
Ribonucleic acid
RNA
RNA modification
Senescence
Translation
TRANSLATIONAL REGULATION
METTL14
TRANSLATIONAL REGULATION
NSUN2
p21 mRNA METHYLATION
METTL3
ISSN:0730-2312, 1097-4644, 1097-4644
Online Access:Get full text
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Summary:ABSTRACT N6‐methyladenosine (m6A) and m5C methylation are two major types of RNA methylation, but the impact of joint modifications on the same mRNA is unknown. Here, we show that in p21 3′UTR, NSUN2 catalyzes m5C modification and METTL3/METTL14 catalyzes m6A modification. Interestingly, methylation at m6A by METTL3/METTL14 facilitates the methylation of m5C by NSUN2, and vice versa. NSUN2‐mediated m5C and METTL3/METTL14‐mediated m6A methylation synergistically enhance p21 expression at the translational level, leading to elevated expression of p21 in oxidative stress‐induced cellular senescence. Our findings on p21 mRNA methylation and expression reveal that joint m6A and m5C modification of the same RNA may influence each other, coordinately affecting protein expression patterns. J. Cell. Biochem. 118: 2587–2598, 2017. © 2017 Wiley Periodicals, Inc. In p21 3'UTR,NSUN2 catalyzes m5C modification and METTL3/METTL14 catalyzes m6A modification. Methylation at m6A by METTL3/METTL14 facilitates the methylation of m5C by NSUN2, and vice versa. NSUN2‐mediated m5C and METTL3/METTL14‐mediated m6A methylation synergistically enhance p21 expression at the translational level, leading to elevated expression of p21 in oxidative stress‐induced cellular senescence.
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These Authors contribute equally to this work
ISSN:0730-2312
1097-4644
1097-4644
DOI:10.1002/jcb.25957