Invertebrate Genetics Laboratory

Saito Group

Molecular mechanisms and physiological functions of epitranscriptome

Faculty

SAITO, Kuniaki
Professor

saitok@nig.ac.jp

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Lab HP

Research Summary

Diverse RNA modifications found in RNA confer novel chemical properties to nucleic acids and regulate functional interactions with various molecules, thereby forming a new layer of epitranscriptomic code. Using the model animal Drosophila and mammalian cultured cells, we aim to elucidate the molecular mechanisms, dynamics, and physiological functions of RNA modifications across various spatiotemporal scales.

(A) Epitranscriptomics is the research area of modifications of RNA molecules by small molecular residues such as methylation. Currently, more than 170 RNA modifications have been identified and studied.
(B) We recently found that Mettl1, one of methyltransferases, is essential for m7G modification and the steady state level of a subset of tRNAs.
(C) Fluorescence image of Drosophila testis isolated from Mettl1-KO. Mettl1-KO males exhibit defects in extended spermatid formation and loses the next generation (Nature Communications 2024).

Selected Publications

  • Kaneko S, Miyoshi K, Tomuro K, Terauchi M, Tanaka R, Kondo S, Tani N, Ishiguro KI, Toyoda A, Kamikouchi A, Noguchi H, Iwasaki S, and Saito K* (2024). Mettl1-dependent m(7)G tRNA modification is essential for maintaining spermatogenesis and fertility in Drosophila melanogaster.　Nat Commun 15, 8147. 10.1038/s41467-024-52389-0.
  • Yamamoto-Matsuda H, Miyoshi K, Moritoh M, Yoshitane H, Fukada Y, Saito K, Yamanaka S, Siomi MC. Lint-O cooperates with L(3)mbt in target gene suppression to maintain homeostasis in fly ovary and brain. EMBO Rep. 2022 Oct 6;23(10):e53813.
  • Utsuno Y, Hamada K, Hamanaka K, Miyoshi K, Tsuchimoto K, Sunada S, Itai T, Sakamoto M, Tsuchida N, Uchiyama Y, Koshimizu E, Fujita A, Miyatake S, Misawa K, Mizuguchi T, Kato Y, Saito K, Ogata K, Matsumoto N. Novel missense variants cause intermediate phenotypes in the phenotypic spectrum of SLC5A6-related disorders. J Hum Genet. 2024 Feb;69(2):69-77.
  • Takeuchi C, Yokoshi M, Kondo S, Shibuya A, Saito K, Fukaya T, Siomi H, Iwasaki YW. Mod(mdg4) variants repress telomeric retrotransposon HeT-A by blocking subtelomeric enhancers. Nucleic Acids Res. 2022 Nov 11;50(20):11580-11599.