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

Hila Toledano, Cecilia D’Alterio, Benjamin Czech, Erel Levine and D. Leanne Jones ()
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Hila Toledano: Laboratory of Genetics, The Salk Institute for Biological Studies
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

Nature, 2012, vol. 485, issue 7400, 605-610

Abstract: 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.

Date: 2012
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DOI: 10.1038/nature11061

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