RRC ID 83698
Author Xu F, Suyama R, Inada T, Kawaguchi S, Kai T.
Title HemK2 functions for sufficient protein synthesis and RNA stability through eRF1 methylation during Drosophila oogenesis.
Journal Development
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.
Volume 151(14)
Published 2024-7-15
DOI 10.1242/dev.202795
PII 357805
PMID 38881530
MeSH Amino Acid Sequence Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster Female Gene Expression Regulation, Developmental Methylation Oogenesis* Peptide Termination Factors* / genetics Peptide Termination Factors* / metabolism RNA Stability* RNA, Messenger / genetics RNA, Messenger / metabolism Sequence Alignment Sequence Homology, Amino Acid Site-Specific DNA-Methyltransferase (Adenine-Specific)* / chemistry Site-Specific DNA-Methyltransferase (Adenine-Specific)* / genetics Site-Specific DNA-Methyltransferase (Adenine-Specific)* / metabolism
IF 5.611
Resource
Drosophila DGRC#104055