| Autor: |
Kaneko, Shunya, Miyoshi, Keita, Tomuro, Kotaro, Terauchi, Makoto, Tanaka, Ryoya, Kondo, Shu, Tani, Naoki, Ishiguro, Kei-Ichiro, Toyoda, Atsushi, Kamikouchi, Azusa, Noguchi, Hideki, Iwasaki, Shintaro, Saito, Kuniaki |
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| Zdroj: |
Nature Communications; 9/24/2024, Vol. 15 Issue 1, p1-17, 17p |
| Abstrakt: |
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. Here the authors reveal essential functions of Mettl1, catalyzing N7-guanosine methylation (m7G) of tRNAs, in Drosophila male fertility through a regulation of the steady-state level of tRNAs and the translational efficiency of genes essential for spermatogenesis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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