HemK2 functions for sufficient protein synthesis and RNA stability through eRF1 methylation during Drosophila oogenesis

Xu, Fengmei; Suyama, Ritsuko; Inada, Toshifumi et al.

Development, 2024, 151(14)

Number of Access:562（2025-09-05 08:59 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/97737

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Title
HemK2 functions for sufficient protein synthesis and RNA stability through eRF1 methylation during Drosophila oogenesis
Creator
CreatorName
Xu, Fengmei
NRID
1000030574652 1000030574652
researchmap permalink
rsuyama rsuyama
ORCID
0000-0001-6154-208X 0000-0001-6154-208X
CreatorName
Suyama, Ritsuko
NRID
1000040242812 1000040242812
CreatorName
Inada, Toshifumi
NRID
1000040321749 1000040321749
researchmap permalink
1234567890abc 1234567890abc
Scopus Author ID
36762092600 36762092600
CreatorName
Kawaguchi, Shinichi
NRID
1000040579786 1000040579786
ORCID
0000-0001-8675-8469 0000-0001-8675-8469
researchmap permalink
toshie_kai toshie_kai
Scopus Author ID
7102037941 7102037941
CreatorName
Kai, Toshie
Subject
Drosophila
eRF1
HemK2 methyltransferase
mRNA surveillance
Oogenesis
Ribosome stalling
Description
Xu F., Suyama R., Inada T., et al. HemK2 functions for sufficient protein synthesis and RNA stability through eRF1 methylation during Drosophila oogenesis. Development 151, (2024); https://doi.org/10.1242/dev.202795.
Abstract
HemK2 is a highly conserved methyltransferase, but the identification of its genuine substrates has been controversial, and its biological importance in higher organisms remains unclear. We elucidate the role of HemK2 in the methylation of eukaryotic Release Factor 1 (eRF1), a process that is essential for female germline development in Drosophila melanogaster. Knockdown of hemK2 in the germline cells (hemK2-GLKD) induces apoptosis, accompanied by a pronounced decrease in both eRF1 methylation and protein synthesis. Overexpression of a methylation-deficient eRF1 variant recapitulates the defects observed in hemK2-GLKD, suggesting that eRF1 is a primary methylation target of HemK2. Furthermore, hemK2-GLKD leads to a significant reduction in mRNA levels in germline cell. These defects in oogenesis and protein synthesis can be partially restored by inhibiting the No-Go Decay pathway. In addition, hemK2 knockdown is associated with increased disome formation, suggesting that disruptions in eRF1 methylation may provoke ribosomal stalling, which subsequently activates translation-coupled mRNA surveillance mechanisms that degrade actively translated mRNAs. We propose that HemK2-mediated methylation of eRF1 is crucial for ensuring efficient protein production and mRNA stability, which are vital for the generation of high-quality eggs.
Publisher
Company of Biologists Ltd
Source Title
Development
Volume (Issue)
151(14)
Date of Issued
2024-07-16
Language
English
Handle URL
https://hdl.handle.net/11094/97737
PISSN
09501991
eISSN
14779129
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1242/dev.202795
Access Rights
open access
oaire:version
Version of Record
Category
学術雑誌論文 Journal Article