Research Papers:

Transcriptome profiling in preadipocytes identifies long noncoding RNAs as Sam68 targets

Naomi Li, Steven Hébert, Jingwen Song, Claudia L. Kleinman and Stéphane Richard _

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Oncotarget. 2017; 8:81994-82005. https://doi.org/10.18632/oncotarget.17813

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Naomi Li1,2,3, Steven Hébert1,4, Jingwen Song1,2,3, Claudia L. Kleinman1,4 and Stéphane Richard1,2,3

1Segal Cancer Center, Sir Mortimer B Davis Jewish General Hospital, Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada

2Department of Medicine, McGill University, Montréal, Québec H3A 1A1, Canada

3Department of Oncology, McGill University, Montréal, Québec H3A 1A1, Canada

4Department of Human Genetics, McGill University, Montréal, Québec H3A 1B1, Canada

Correspondence to:

Stéphane Richard, email: [email protected]

Keywords: Sam68, RNA binding proteins, lncRNAs, preadipocytes, adipogenesis

Received: January 05, 2017    Accepted: April 17, 2017    Published: May 11, 2017


The KH-type RNA binding protein Sam68 is required for adipogenesis. We have previously shown that Sam68-deficient mice have a lean phenotype and are protected against dietary-induced obesity due to defects in mTOR and S6K1 alternative splicing. Herein we profiled the transcriptome of Sam68 wild type and deficient 3T3-L1 mouse preadipocytes. We identified 652 protein-coding genes and 9 ncRNAs that were significantly altered with the loss of Sam68. As expected, downregulated genes were significantly associated with GO terms linked to cell migration, motility, and fat cell differentiation, while upregulated genes were mostly associated with GO terms linked to neurogenesis. Of the lncRNAs, we identified Hotair, Mir155hg, as well as two new lncRNAs (SR-lncRNA-1 and SR-lncRNA-2) that were regulated by Sam68, and contained consensus Sam68 binding sites. RNA stability assays showed that Sam68-deficiency decreased the half-life of Hotair, and increased the half-lives of Mir155hg and SR-lncRNA-2, while the stability of SR-lncRNA-1 was unaffected. Depletion of Hotair and SR-lncRNA-1 in wild type 3T3-L1 cells led to defects in adipogenesis, whereas depletion of SR-lncRNA-2 in Sam68-deficient 3T3-L1 cells partially rescued the adipogenesis defect observed in these cells. Collectively, our findings define a new role for Sam68 as a regulator of lncRNAs during adipogenic differentiation.

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