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

Shunya Kaneko, Keita Miyoshi, Kotaro Tomuro, Makoto Terauchi, Ryoya Tanaka, Shu Kondo, Naoki Tani, Kei-Ichiro Ishiguro, Atsushi Toyoda, Azusa Kamikouchi, Hideki Noguchi, Shintaro Iwasaki, and Kuniaki Saito

Nature Communications (2024) 15,  8147 DOI:10.1038/s41467-024-52389-0

Press release (In Japanese only)

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 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 m7G 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 m7G tRNA modification and indicate that m7G modification-dependent tRNA abundance differs among tissues.

On September 10, 2024, Mr. Biswa, Bhim Bahadur (Mouse Genomics Resource Laboratory, Koide Laboratory) received the Morishima Award from the Genetics Program, SOKENDAI.
The Morishima Award is given to students in the Genetics Program to honor their outstanding performances during PhD studies and to encourage further achievements.

・Biswa, Bhim Bahadur (Mouse Genomics Resource Laboratory, thesis advisor: Koide Tsuyoshi)
thesis title :  Role of gut bacteria in domestication of mice

▶ The Morishima Award

▶ — Professor Emeritus — MORISHIMA, Hiroko

• Awarded presentation title: Chromatin organization and behavior in HRAS-transformed mouse fibroblasts.
• Physical Models of Living Matters – The 3rd Symposium of Physical Biology and Biological Physics
• Genome Dynamics Laboratory