Kaneko, S., Miyoshi, K., Tomuro, K., Terauchi, M., Tanaka, R., Kondo, S., Tani, N., Ishiguro, K.I., Toyoda, A., Kamikouchi, A., Noguchi, H., Iwasaki, S., Saito, K. (2024). Mettl1-dependent m[7]G tRNA modification is essential for maintaining spermatogenesis and fertility in Drosophila melanogaster.  Nat. Commun. 15(1): 8147.

FBrf0260508

Research paper

Modification of guanosine to N[7]-methylguanosine (m[7]G) 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 m[7]G is required for spermatogenesis. Mettl1-KO results in a loss of m[7]G modification on a subset of tRNAs and decreased tRNA abundance. Ribosome profiling shows that Mettl1-KO led to ribosomes stalling at codons decoded by tRNAs that were reduced in abundance. Mettl1-KO also significantly reduces the translation efficiency of genes involved in elongated spermatid formation and sperm stability. Germ cell-specific expression of Mettl1 rescues disrupted m[7]G tRNA modification and tRNA abundance in Mettl1-KO testes but not in non-gonadal tissues. Ribosome stalling is much less detectable in non-gonadal tissues than in Mettl1-KO testes. These findings reveal a developmental role for m[7]G tRNA modification and indicate that m[7]G modification-dependent tRNA abundance differs among tissues.

PMC11422498 (PMC) (EuropePMC)