Molecular Mechanisms Driving mRNA Degradation by m6A Modification

Yujin Lee; Junho Choe; Ok Hyun Park; Yoon Ki Kim

doi:10.1016/j.tig.2019.12.007

Molecular Mechanisms Driving mRNA Degradation by m⁶A Modification

Yujin Lee
, Junho Choe
, Ok Hyun Park
, Yoon Ki Kim^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

341 Citations (Scopus)

Abstract

N⁶-Methyladenosine (m⁶A), the most prevalent internal modification associated with eukaryotic mRNAs, influences many steps of mRNA metabolism, including splicing, export, and translation, as well as stability. Recent studies have revealed that m⁶A-containing mRNAs undergo one of two distinct pathways of rapid degradation: deadenylation via the YT521-B homology (YTH) domain-containing family protein 2 (YTHDF2; an m⁶A reader protein)–CCR4/NOT (deadenylase) complex or endoribonucleolytic cleavage by the YTHDF2–HRSP12–ribonuclease (RNase) P/mitochondrial RNA-processing (MRP) (endoribonuclease) complex. Some m⁶A-containing circular RNAs (circRNAs) are also subject to endoribonucleolytic cleavage by YTHDF2–HRSP12–RNase P/MRP. Here, we highlight recent progress on the molecular mechanisms underlying rapid mRNA degradation via m⁶A and describe our current understanding of the dynamic regulation of m⁶A-mediated mRNA decay through the crosstalk between m⁶A (or YTHDF2) and other cellular factors.

Original language	English
Pages (from-to)	177-188
Number of pages	12
Journal	Trends in Genetics
Volume	36
Issue number	3
DOIs	https://doi.org/10.1016/j.tig.2019.12.007
Publication status	Published - 2020 Mar

Bibliographical note

Publisher Copyright:
© 2019 The Authors

Keywords

HRSP12
RNase P/MRP
YTHDF2
circular RNA
endoribonucleolytic cleavage
mA modification

ASJC Scopus subject areas

Genetics

Access to Document

10.1016/j.tig.2019.12.007

Cite this

@article{8f656dd782174d2a9352965f456f5600,

title = "Molecular Mechanisms Driving mRNA Degradation by m6A Modification",

abstract = "N6-Methyladenosine (m6A), the most prevalent internal modification associated with eukaryotic mRNAs, influences many steps of mRNA metabolism, including splicing, export, and translation, as well as stability. Recent studies have revealed that m6A-containing mRNAs undergo one of two distinct pathways of rapid degradation: deadenylation via the YT521-B homology (YTH) domain-containing family protein 2 (YTHDF2; an m6A reader protein)–CCR4/NOT (deadenylase) complex or endoribonucleolytic cleavage by the YTHDF2–HRSP12–ribonuclease (RNase) P/mitochondrial RNA-processing (MRP) (endoribonuclease) complex. Some m6A-containing circular RNAs (circRNAs) are also subject to endoribonucleolytic cleavage by YTHDF2–HRSP12–RNase P/MRP. Here, we highlight recent progress on the molecular mechanisms underlying rapid mRNA degradation via m6A and describe our current understanding of the dynamic regulation of m6A-mediated mRNA decay through the crosstalk between m6A (or YTHDF2) and other cellular factors.",

keywords = "HRSP12, RNase P/MRP, YTHDF2, circular RNA, endoribonucleolytic cleavage, mA modification",

author = "Yujin Lee and Junho Choe and Park, \{Ok Hyun\} and Kim, \{Yoon Ki\}",

note = "Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2020",

month = mar,

doi = "10.1016/j.tig.2019.12.007",

language = "English",

volume = "36",

pages = "177--188",

journal = "Trends in Genetics",

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TY - JOUR

T1 - Molecular Mechanisms Driving mRNA Degradation by m6A Modification

AU - Lee, Yujin

AU - Choe, Junho

AU - Park, Ok Hyun

AU - Kim, Yoon Ki

PY - 2020/3

Y1 - 2020/3

N2 - N6-Methyladenosine (m6A), the most prevalent internal modification associated with eukaryotic mRNAs, influences many steps of mRNA metabolism, including splicing, export, and translation, as well as stability. Recent studies have revealed that m6A-containing mRNAs undergo one of two distinct pathways of rapid degradation: deadenylation via the YT521-B homology (YTH) domain-containing family protein 2 (YTHDF2; an m6A reader protein)–CCR4/NOT (deadenylase) complex or endoribonucleolytic cleavage by the YTHDF2–HRSP12–ribonuclease (RNase) P/mitochondrial RNA-processing (MRP) (endoribonuclease) complex. Some m6A-containing circular RNAs (circRNAs) are also subject to endoribonucleolytic cleavage by YTHDF2–HRSP12–RNase P/MRP. Here, we highlight recent progress on the molecular mechanisms underlying rapid mRNA degradation via m6A and describe our current understanding of the dynamic regulation of m6A-mediated mRNA decay through the crosstalk between m6A (or YTHDF2) and other cellular factors.

AB - N6-Methyladenosine (m6A), the most prevalent internal modification associated with eukaryotic mRNAs, influences many steps of mRNA metabolism, including splicing, export, and translation, as well as stability. Recent studies have revealed that m6A-containing mRNAs undergo one of two distinct pathways of rapid degradation: deadenylation via the YT521-B homology (YTH) domain-containing family protein 2 (YTHDF2; an m6A reader protein)–CCR4/NOT (deadenylase) complex or endoribonucleolytic cleavage by the YTHDF2–HRSP12–ribonuclease (RNase) P/mitochondrial RNA-processing (MRP) (endoribonuclease) complex. Some m6A-containing circular RNAs (circRNAs) are also subject to endoribonucleolytic cleavage by YTHDF2–HRSP12–RNase P/MRP. Here, we highlight recent progress on the molecular mechanisms underlying rapid mRNA degradation via m6A and describe our current understanding of the dynamic regulation of m6A-mediated mRNA decay through the crosstalk between m6A (or YTHDF2) and other cellular factors.

KW - HRSP12

KW - RNase P/MRP

KW - YTHDF2

KW - circular RNA

KW - endoribonucleolytic cleavage

KW - mA modification

UR - https://www.scopus.com/pages/publications/85077927431

U2 - 10.1016/j.tig.2019.12.007

DO - 10.1016/j.tig.2019.12.007

M3 - Review article

C2 - 31964509

AN - SCOPUS:85077927431

SN - 0168-9525

VL - 36

SP - 177

EP - 188

JO - Trends in Genetics

JF - Trends in Genetics

IS - 3

ER -