eRF1 methylation by HemK2 modulates protein synthesis and mRNA stability during Drosophila oogenesis.

HemK2 is a well conserved methyltransferase. In Drosophila melanogaster, germline-specific knockdown of hemk2 (hemk2-GLKD) resulted in apoptosis, leading to developmental arrest during mid-oogenesis and subsequent female sterility. A significant reduction in eRF1 methylation accompanied hemk2-GLKD, highlighting the importance of HemK2 in this modification process. Moreover, the phenotypic defects observed in hemk2-GLKD were recapitulated by the overexpression of a transgene with impaired eRF1 methylation, further supporting the role of HemK2 in this context. Utilizing the protein synthesis assay, we discovered that hemk2-GLKD led to a substantial decrease in translational efficiency, potentially due to disruptions in the proper release of synthesized peptides at stop codons. Concurrently, hemk2-GLKD caused a severe reduction in mRNA levels. Notably, the defects observed in hemk2-GLKD were ameliorated by blocking the no-go decay (NGD) pathway, emphasizing the involvement of this pathway in mitigating the consequences of HemK2 depletion. We propose that HemK2-mediated eRF1 methylation is essential for both efficient protein production and mRNA stability, ensuring the proper progression of Drosophila oogenesis.