m6A sites in the coding region trigger translation-dependent
mRNA decay

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m6A sites in the coding region trigger translation-dependent mRNA decay

Přehled o publikaci

J 2024

m6A sites in the coding region trigger translation-dependent mRNA decay

ZHOU, You; Miona COROVIC; Peter HOCH-KRAFT; Nathalie MEISER; Mikhail MESITOV et. al.

Basic information

Original name

m6A sites in the coding region trigger translation-dependent mRNA decay

Authors

Edition

Molecular Cell, CAMBRIDGE, CELL PRESS, 2024, 1097-2765

Other information

Language

English

Type of outcome

Article in a journal

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Organization

Středoevropský technologický institut – Repository – Repository

DOI

http://dx.doi.org/10.1016/j.molcel.2024.10.033

UT WoS

001374737200001

EID Scopus

2-s2.0-85210724639

Keywords in English

CODON OPTIMALITY; QUALITY-CONTROL; TRANSCRIPTOME; METHYLATION; REVEALS; PURIFICATION; ELONGATION; SELECTION

Links

EH22_008/0004575, research and development project. GA22-12871S, research and development project. CIISB III, large research infrastructures. e-INFRA CZ II, large research infrastructures. NCMG III, large research infrastructures.

Changed: 18/3/2025 00:51, RNDr. Daniel Jakubík

Abstract

V originále

N6-Methyladenosine (m6A) is the predominant internal RNA modification in eukaryotic messenger RNAs (mRNAs) and plays a crucial role in mRNA stability. Here, using human cells, we reveal that m6A sites in the coding sequence (CDS) trigger CDS-m6A decay (CMD), a pathway that is distinct from previously reported m6A-dependent degradation mechanisms. Importantly, CDS m6A sites act considerably faster and more efficiently than those in the 30 untranslated region, which to date have been considered the main effectors. Mechanistically, CMD depends on translation, whereby m6A deposition in the CDS triggers ribosome pausing and transcript destabilization. The subsequent decay involves the translocation of the CMD target transcripts to processing bodies (P-bodies) and recruitment of the m6A reader protein YT521-B homology domain family protein 2 (YTHDF2). Our findings highlight CMD as a previously unknown pathway, which is particularly important for controlling the expression of developmental regulators and retrogenes.

Files attached

https://is.muni.cz/publication/2461897/1-s2.0-S1097276524008736-main.pdf

Cite

ZHOU, You; Miona COROVIC; Peter HOCH-KRAFT; Nathalie MEISER; Mikhail MESITOV; Nadine KOERTEL; Hannah BACK; Vries Isabel S NAARMANN-DE; Kritika Suresh KATTI; Aleš OBRDLÍK; Anke BUSCH; Christoph DIETERICH; Štěpánka VAŇÁČOVÁ; Martin HENGESBACH; Kathi ZARNACK and Julian KOENIG. m6A sites in the coding region trigger translation-dependent mRNA decay. Molecular Cell. CAMBRIDGE: CELL PRESS, 2024, vol. 84, No 23, p. 1-31. ISSN 1097-2765. Available from: https://dx.doi.org/10.1016/j.molcel.2024.10.033.

@article{65827,
   author = {Zhou, You and Corovic, Miona and HochandKraft, Peter and Meiser, Nathalie and Mesitov, Mikhail and Koertel, Nadine and Back, Hannah and Naarmannandde, Vries Isabel S and Katti, Kritika Suresh and Obrdlík, Aleš and Busch, Anke and Dieterich, Christoph and Vaňáčová, Štěpánka and Hengesbach, Martin and Zarnack, Kathi and Koenig, Julian},
   article_location = {CAMBRIDGE},
   article_number = {23},
   doi = {http://dx.doi.org/10.1016/j.molcel.2024.10.033},
   keywords = {CODON OPTIMALITY; QUALITY-CONTROL; TRANSCRIPTOME; METHYLATION; REVEALS; PURIFICATION; ELONGATION; SELECTION},
   language = {eng},
   issn = {1097-2765},
   journal = {Molecular Cell},
   title = {m6A sites in the coding region trigger translation-dependent mRNA decay},
   url = {https://www.sciencedirect.com/science/article/pii/S1097276524008736?via%3Dihub},
   volume = {84},
   year = {2024}
}

TY  - JOUR
ID  - 65827
AU  - Zhou, You - Corovic, Miona - Hoch-Kraft, Peter - Meiser, Nathalie - Mesitov, Mikhail - Koertel, Nadine - Back, Hannah - Naarmann-de, Vries Isabel S - Katti, Kritika Suresh - Obrdlík, Aleš - Busch, Anke - Dieterich, Christoph - Vaňáčová, Štěpánka - Hengesbach, Martin - Zarnack, Kathi - Koenig, Julian
PY  - 2024
TI  - m6A sites in the coding region trigger translation-dependent mRNA decay
JF  - Molecular Cell
VL  - 84
IS  - 23
SP  - 1-31
EP  - 1-31
PB  - CELL PRESS
SN  - 1097-2765
KW  - CODON OPTIMALITY
KW  - QUALITY-CONTROL
KW  - TRANSCRIPTOME
KW  - METHYLATION
KW  - REVEALS
KW  - PURIFICATION
KW  - ELONGATION
KW  - SELECTION
UR  - https://www.sciencedirect.com/science/article/pii/S1097276524008736?via%3Dihub
N2  - N6-Methyladenosine (m6A) is the predominant internal RNA modification in eukaryotic messenger RNAs (mRNAs) and plays a crucial role in mRNA stability. Here, using human cells, we reveal that m6A sites in the coding sequence (CDS) trigger CDS-m6A decay (CMD), a pathway that is distinct from previously reported m6A-dependent degradation mechanisms. Importantly, CDS m6A sites act considerably faster and more efficiently than those in the 30 untranslated region, which to date have been considered the main effectors. Mechanistically, CMD depends on translation, whereby m6A deposition in the CDS triggers ribosome pausing and transcript destabilization. The subsequent decay involves the translocation of the CMD target transcripts to processing bodies (P-bodies) and recruitment of the m6A reader protein YT521-B homology domain family protein 2 (YTHDF2). Our findings highlight CMD as a previously unknown pathway, which is particularly important for controlling the expression of developmental regulators and retrogenes.
ER  -

ZHOU, You; Miona COROVIC; Peter HOCH-KRAFT; Nathalie MEISER; Mikhail MESITOV; Nadine KOERTEL; Hannah BACK; Vries Isabel S NAARMANN-DE; Kritika Suresh KATTI; Aleš OBRDLÍK; Anke BUSCH; Christoph DIETERICH; Štěpánka VAŇÁČOVÁ; Martin HENGESBACH; Kathi ZARNACK and Julian KOENIG. m6A sites in the coding region trigger translation-dependent mRNA decay. \textit{Molecular Cell}. CAMBRIDGE: CELL PRESS, 2024, vol.~84, No~23, p.~1-31. ISSN~1097-2765. Available from: https://dx.doi.org/10.1016/j.molcel.2024.10.033.