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

Author

Listed:
  • Shunya Kaneko

    (Research Organization of Information and Systems (ROIS)
    SOKENDAI)

  • Keita Miyoshi

    (Research Organization of Information and Systems (ROIS)
    SOKENDAI)

  • Kotaro Tomuro

    (RIKEN Cluster for Pioneering Research
    The University of Tokyo)

  • Makoto Terauchi

    (Research Organization of Information and Systems (ROIS))

  • Ryoya Tanaka

    (Nagoya University
    Nagoya University)

  • Shu Kondo

    (Tokyo University of Science)

  • Naoki Tani

    (Kumamoto University)

  • Kei-Ichiro Ishiguro

    (Kumamoto University)

  • Atsushi Toyoda

    (Research Organization of Information and Systems (ROIS))

  • Azusa Kamikouchi

    (Nagoya University
    Nagoya University
    Nagoya University)

  • Hideki Noguchi

    (Research Organization of Information and Systems (ROIS))

  • Shintaro Iwasaki

    (RIKEN Cluster for Pioneering Research
    The University of Tokyo)

  • Kuniaki Saito

    (Research Organization of Information and Systems (ROIS)
    SOKENDAI)

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.

Suggested Citation

  • 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 & , 2024. "Mettl1-dependent m7G tRNA modification is essential for maintaining spermatogenesis and fertility in Drosophila melanogaster," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52389-0
    DOI: 10.1038/s41467-024-52389-0
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    References listed on IDEAS

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