論文 - 詳細
| RRC ID | 81884 |
|---|---|
| 著者 | Kaneko S, Miyoshi K, Tomuro K, Terauchi M, Tanaka R, Kondo S, Tani N, Ishiguro KI, Toyoda A, Kamikouchi A, Noguchi H, Iwasaki S, Saito K. |
| タイトル | Mettl1-dependent m7G tRNA modification is essential for maintaining spermatogenesis and fertility in Drosophila melanogaster. |
| ジャーナル | Nat Commun |
| 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 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. |
| 巻・号 | 15(1) |
| ページ | 8147 |
| 公開日 | 2024-9-24 |
| DOI | 10.1038/s41467-024-52389-0 |
| PII | 10.1038/s41467-024-52389-0 |
| PMID | 39317727 |
| PMC | PMC11422498 |
| MeSH | Animals Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster* / genetics Drosophila melanogaster* / metabolism Fertility* / genetics Gene Knockout Techniques Guanosine / analogs & derivatives Guanosine / metabolism Male Methyltransferases / genetics Methyltransferases / metabolism RNA, Transfer* / genetics RNA, Transfer* / metabolism Ribosomes / metabolism Spermatids / metabolism Spermatogenesis* / genetics Spermatozoa / metabolism Testis / metabolism |
| IF | 12.121 |
| リソース情報 | |
| ショウジョウバエ | 10009Ab-1 DGRC#118616 |