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The let-7–Imp axis regulates ageing of the Drosophila testis stem-cell niche

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  • Hila Toledano

    (Laboratory of Genetics, The Salk Institute for Biological Studies
    Present address: Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Mount Carmel, Haifa 31905, Israel.)

  • Cecilia D’Alterio

    (Laboratory of Genetics, The Salk Institute for Biological Studies)

  • Benjamin Czech

    (Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA)

  • Erel Levine

    (Harvard University)

  • D. Leanne Jones

    (Laboratory of Genetics, The Salk Institute for Biological Studies)

Abstract

Adult stem cells support tissue homeostasis and repair throughout the life of an individual. During ageing, numerous intrinsic and extrinsic changes occur that result in altered stem-cell behaviour and reduced tissue maintenance and regeneration. In the Drosophila testis, ageing results in a marked decrease in the self-renewal factor Unpaired (Upd), leading to a concomitant loss of germline stem cells. Here we demonstrate that IGF-II messenger RNA binding protein (Imp) counteracts endogenous small interfering RNAs to stabilize upd (also known as os) RNA. However, similar to upd, Imp expression decreases in the hub cells of older males, which is due to the targeting of Imp by the heterochronic microRNA let-7. In the absence of Imp, upd mRNA therefore becomes unprotected and susceptible to degradation. Understanding the mechanistic basis for ageing-related changes in stem-cell behaviour will lead to the development of strategies to treat age-onset diseases and facilitate stem-cell-based therapies in older individuals.

Suggested Citation

  • Hila Toledano & Cecilia D’Alterio & Benjamin Czech & Erel Levine & D. Leanne Jones, 2012. "The let-7–Imp axis regulates ageing of the Drosophila testis stem-cell niche," Nature, Nature, vol. 485(7400), pages 605-610, May.
  • Handle: RePEc:nat:nature:v:485:y:2012:i:7400:d:10.1038_nature11061
    DOI: 10.1038/nature11061
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    Cited by:

    1. 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.

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