Saito Group • Invertebrate Genetics Laboratory::National Institute of Genetics

Saito Group • Invertebrate Genetics Laboratory

Epitranscriptomics in Drosophila

Faculty

SAITO, Kuniaki

Professor

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MIYOSHI, Keita

Assistant Professor

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Research Summary

RNA acts as not only a carrier of genetic information but also a highly versatile molecule that can be cut, connected, and dramatically change its steric structure. Our laboratory is studying molecular mechanisms and physiological functions of RNA-based gene regulation in Drosophila. To understand them, we are currently engaged in investigating the physiological functions and molecular mechanisms of RNA modifications (epitranscriptome) using biochemical and high-throughput technologies, and genetic tools which are managed and distributed by genetic resources project (NIG-Fly).

(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, Saito K. Mettl1-dependent m⁷G tRNA modification is essential for maintaining spermatogenesis and fertility in Drosophila melanogaster. Nat Commun. 2024 Sep 24;15(1):8147.

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.