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

Hila Toledano; Cecilia D'Alterio; Benjamin Czech; Erel Levine; D. Leanne Jones

doi:10.1038/nature11061

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

Hila Toledano, Cecilia D'Alterio, Benjamin Czech, Erel Levine, D. Leanne Jones

Department of Human Biology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	605-610
Number of pages	6
Journal	Nature
Volume	485
Issue number	7400
DOIs	https://doi.org/10.1038/nature11061
State	Published - 2012

Bibliographical note

Funding Information:
Acknowledgements We are grateful to D. St Johnston, W. Chia, P. Macdonald, R. Carthew, E. Bach, D. Harrison, T. Volk, U. Heberlein, A. Spradling, J. Kadonaga, G. Hannon, T. Hays, N. Sokol, H. Siomi andP. Lasko for reagents and flystocks, to C. Doe, R. Hans, G. Volohonsky, T. Juven-Gershon, A. Pasquinelli, R. Zhou and S. Aigner for guidance on methods used in this manuscript, to O. Tam for computational support, and to C. Koehler for technical assistance. This work was supported by the G. Harold and Leila Y. Mathers Charitable Foundation, the Ellison Medical Foundation, the Emerald Foundation, the American Federation for Aging Research, and the National InstitutesofHealth(to D.L.J.).B.C. issupported byaPhD fellowshipfromthe Boehringer Ingelheim Fonds. E.L. is supported by the National Science Foundation.

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title = "The let-7-Imp axis regulates ageing of the Drosophila testis stem-cell niche",

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.",

author = "Hila Toledano and Cecilia D'Alterio and Benjamin Czech and Erel Levine and Jones, {D. Leanne}",

note = "Funding Information: Acknowledgements We are grateful to D. St Johnston, W. Chia, P. Macdonald, R. Carthew, E. Bach, D. Harrison, T. Volk, U. Heberlein, A. Spradling, J. Kadonaga, G. Hannon, T. Hays, N. Sokol, H. Siomi andP. Lasko for reagents and flystocks, to C. Doe, R. Hans, G. Volohonsky, T. Juven-Gershon, A. Pasquinelli, R. Zhou and S. Aigner for guidance on methods used in this manuscript, to O. Tam for computational support, and to C. Koehler for technical assistance. This work was supported by the G. Harold and Leila Y. Mathers Charitable Foundation, the Ellison Medical Foundation, the Emerald Foundation, the American Federation for Aging Research, and the National InstitutesofHealth(to D.L.J.).B.C. issupported byaPhD fellowshipfromthe Boehringer Ingelheim Fonds. E.L. is supported by the National Science Foundation.",

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

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