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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Argonaute Proteins / metabolism
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Base Sequence
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Cellular Senescence / physiology*
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Drosophila Proteins / biosynthesis
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / cytology*
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Drosophila melanogaster / genetics
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Drosophila melanogaster / metabolism*
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Female
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Male
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MicroRNAs / genetics*
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Organ Specificity
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RNA Helicases / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Small Interfering / antagonists & inhibitors
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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RNA-Binding Proteins / biosynthesis
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism*
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Ribonuclease III / metabolism
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Stem Cell Niche / genetics
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Stem Cell Niche / physiology*
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Testis / cytology*
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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AGO2 protein, Drosophila
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Argonaute Proteins
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Drosophila Proteins
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Imp protein, Drosophila
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Let-7 microRNA, Drosophila
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MicroRNAs
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RNA, Messenger
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RNA, Small Interfering
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RNA-Binding Proteins
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Transcription Factors
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upd1 protein, Drosophila
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DCR-2 protein, Drosophila
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Ribonuclease III
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RNA Helicases