| First Author | Chi YL | Year | 2018 |
| Journal | Biochim Biophys Acta Mol Cell Res | Volume | 1865 |
| Issue | 11 Pt A | Pages | 1515-1525 |
| PubMed ID | 30327195 | Mgi Jnum | J:318872 |
| Mgi Id | MGI:6863626 | Doi | 10.1016/j.bbamcr.2018.08.001 |
| Citation | Chi YL, et al. (2018) RBM4a modulates the impact of PRDM16 on development of brown adipocytes through an alternative splicing mechanism. Biochim Biophys Acta Mol Cell Res 1865(11 Pt A):1515-1525 |
| abstractText | Brown adipocytes (BAs) exhibit an energy-expending signature that is important in balancing metabolic homeostasis. In this study, results of transcriptome analyses revealed the reprogrammed splicing profile of the PR domain containing 16 (PRDM16) gene, a key transcription factor involved in brown adipogenesis, throughout development of wild-type brown adipose tissues (BATs). Moreover, discriminative splicing patterns of PRDM16 transcripts were noted in embryonic and postnatal RBM4a(-/-) BATs. Overexpression of RBM4a enhanced the relative levels of PRDM16(-ex 16) transcripts by simultaneously interacting with exonic and intronic CU elements, which encoded the PRDM16S isoform containing a distinct C-terminus. The presence of the overexpressed PRDM16S isoform showed a stronger effect than the overexpressed PRDM16L isoform on enhancing transcriptional activity of the RBM4a and the PGC-1alpha promoter. Overexpression of the PRDM16S isoform exerted more-prominent effects on enhancing the BAT-related gene program and energy expenditure compared to those of PRDM16L-overexpressing cells. Our studies demonstrated that RBM4a-regulated alternative splicing constituted another regulatory mechanism for strengthening the influence of PRDM16 on the development of brown adipocytes. |
