Mettl1-dependent m⁷G tRNA modification is essential for maintaining spermatogenesis and fertility in Drosophila melanogaster.

ABSTRACT: Modification of guanosine to N⁷-methylguanosine (m⁷G) in the variable loop region of tRNA is catalyzed by the METTL1/WDR4 heterodimer and stabilizes target tRNA. Here, we reveal essential functions of Mettl1 in Drosophila fertility. Knockout of Mettl1 (Mettl1-KO) causes no major effect on the development of non-gonadal tissues, but abolishes the production of elongated spermatids and mature sperm, which is fully rescued by expression of a Mettl1-transgene, but not a catalytic-dead Mettl1 transgene. This demonstrates that Mettl1-dependent m⁷G is required for spermatogenesis. Mettl1-KO results in a loss of m⁷G modification on a subset of tRNAs and decreased tRNA abundance. Ribosome profiling shows that Mettl1-KO led to ribosomes stalling at codons

SUBMITTER: Kaneko S 

PROVIDER: S-EPMC11422498 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature