ゲノムの「暴れ者」トランスポゾンを押さえ込むしなやかな戦略~piRNAの増幅経路が持つもう一つの役割~

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2025-03-21 東京大学,東京農工大学

東京大学定量生命科学研究所の研究チームは、エンハンサー領域での非コードRNAの転写が、遺伝子の転写量を抑制する新たなメカニズムを発見しました。エンハンサー上での非コードRNAの転写が、転写因子の結合を物理的に妨げることで、遺伝子の発現を制御することが明らかになりました。この成果は、遺伝子発現制御の新たな理解を提供し、将来的な遺伝子治療や創薬研究に貢献する可能性があります。

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隣接するピンポン増幅部位間の競合によるpiRNA配列レパートリーの自律的形成 Autonomous shaping of the piRNA sequence repertoire by competition between adjacent ping-pong amplification sites

Jie Yu (喻婕) ∙ Fumiko Kawasaki (河﨑 史子) ∙ Natsuko Izumi (泉 奈津子) ∙ … ∙ Susumu Katsuma (勝間 進) ∙ Yukihide Tomari (泊 幸秀) ∙ Keisuke Shoji (庄司 佳祐)
Molecular Cell  Accepted: February 19, 2025
DOI:https://doi.org/10.1016/j.molcel.2025.02.015

Graphical abstract

ゲノムの「暴れ者」トランスポゾンを押さえ込むしなやかな戦略~piRNAの増幅経路が持つもう一つの役割~

Highlights

  • piRNA sequence repertoires in silkworm cells change dynamically over time
  • The repertoire changeability negatively correlates with piRNA biogenesis efficiency
  • Competition between adjacent amplification sites optimizes the piRNA repertoire
  • piRNAs autonomously avoid deleterious mismatches in target recognition

Summary

PIWI-interacting RNAs (piRNAs) are crucial for silencing transposable elements (TEs). In many species, piRNAs are generated via a complex process known as the ping-pong pathway, coupling TE cleavage with piRNA amplification. However, the biological significance of this complexity remains unclear. Here, we systematically compared piRNA profiles in two related silkworm cell lines and found significant changes in their sequence repertoire. Importantly, the changeability of this repertoire negatively correlated with the piRNA biogenesis efficiency, a trend also observed in Drosophila stocks and single silkworm eggs. This can be explained by competition between adjacent ping-pong sites, supported by our mathematical modeling. Moreover, this competition can rationalize how piRNAs autonomously avoid deleterious mismatches to target TEs in silkworms, flies, and mice. These findings unveil the intrinsic plasticity and adaptability of the piRNA system to combat diverse TE sequences and highlight the universal power of competition and self-amplification to drive autonomous optimization.

生物工学一般
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