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.