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Metformin Induces Dicer via Regulation of the RNA-binding protein AUF1

ABSTRACT: Metformin has been commonly used for decades to treat type 2 diabetes. Recent data indicates that mice treated with metformin live longer and healthier lives. Here, we show that chronic metformin exposure in mice and diabetics taking metformin have higher levels of the microRNA processing protein, Dicer. Examination of how metformin affects Dicer expression revealed that metformin alters binding of the AUF1 RNA-binding protein to DICER1 mRNA, which leads to stabilization of DICER1 mRNA. We found differential changes in microRNA expression in mice treated with metformin or caloric restriction, a proven life extending intervention. Several of these microRNAs are important for regulating cellular senescence and lifespan in model organisms. Consistent with this observation, treatment with metformin decreased cellular senescence in a Dicer-dependent manner. These data lead us to hypothesize that changes in Dicer levels may be important for organismal aging and that interventions that upregulate Dicer expression (e.g., metformin) may offer new therapeutic approaches to combat or prevent age-related diseases. Key words: diabetes mellitus, metformin, senescence, miRNA, RNA-binding proteins

ORGANISM(S): Mus musculus

PROVIDER: GSE73393 | GEO | 2017/02/14

SECONDARY ACCESSION(S): PRJNA296876

REPOSITORIES: GEO

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2023-03-10 | PXD021094 | Pride

WT and AUF1 KO satellite cell RNA-sequencing

2016-07-21 | E-GEOD-83555 | biostudies-arrayexpress

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Project description:We report that AUF1 modulates global mRNA stability and translation, in turn promoting the maintenance of DNA integrity. Please see individual series. In short, For AUF1 PAR-CLIP, the four isoforms of AUF1 (p37, p40, p42, and p45) tagged with a Flag epitope were expressed in HEK293 cells. For total RNA-Seq HEK293 cells were transfected with Control siRNA, AUF1 siRNA, Empty Vector, Flag-AUF1 p37, p40, p42, or p45 as well as WI-38 cells were collected at PDL 15 and 55 and also transfected with Control siRNA, AUF1 siRNA, HuR siRNA. For Ribo-Seq HeLa cells were transfected with Control siRNA, AUF1 siRNA, or HuR siRNA.

2014-11-04 | E-GEOD-52976 | biostudies-arrayexpress

Integrative AUF1 PAR-CLIP analysis uncovers AUF1 roles in translation and genome integrity (PAR-CLIP)

Project description:We report that AUF1 modulates global mRNA stability and translation, in turn promoting the maintenance of DNA integrity. Please see individual series. In short, for AUF1 PAR-CLIP, the four isoforms of AUF1 (p37, p40, p42, and p45) tagged with a Flag epitope were expressed in HEK293 cells. For total RNA-Seq HEK293 cells were transfected with Control siRNA, AUF1 siRNA, Empty Vector, Flag-AUF1 p37, p40, p42, or p45 as well as WI-38 cells were collected at PDL 15 and 55 and also transfected with Control siRNA, AUF1 siRNA, HuR siRNA. For Ribo-Seq HeLa cells were transfected with Control siRNA, AUF1 siRNA, or HuR siRNA.

2014-11-05 | E-GEOD-52971 | biostudies-arrayexpress

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2015-09-30 | GSE64761 | GEO

Concurrent Versus Individual Binding of HuR and AUF1 to Common Labile Target mRNAs

Project description:RNA was isolated from material that had been immunoprecipitated (IP) from Hela cells using antibodies recognizing RNA-binding proteins HuR or AUF1, as well as using a control IgG1 antibody. RNA was reverse-transcribed in the presence of [alpha-33P]dCTP and the radiolabeled product used to hybridize human cDNA arrays. The experiment was repeated using three independent sample sets. The samples were numbered HuR-1, HuR-2, HuR-3, AUF1-1, AUF1-2, AUF1-3, IgG1-1, IgG1-2, IgG1-3. HuR represents RNA from IP reactions using an anti-HuR antibody, AUF1 represents RNA from IP reactions using an anti-AUF1 antibody and, IgG1 represents RNA from IP reactions using an anti-IgG1 antibody. The numbers 1, 2 and 3 correspond to the three independent experimental datasets. Keywords = RNa-binding protein Keywords = mRNA stability Keywords = exosome Keywords = polysome Keywords = RNA motif Keywords: ordered

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2014-11-04 | E-GEOD-52975 | biostudies-arrayexpress

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