TY - JOUR
T1 - RBM4a modulates the impact of PRDM16 on development of brown adipocytes through an alternative splicing mechanism
AU - Chi, Yi Lin
AU - Lin, Jung Chun
N1 - Funding Information:
This work was supported by a grant ( MOST106-2320-B-038-059 ) from the Ministry of Science and Technology, Taiwan . The authors declare that no competing interests exist.
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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-1α 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.
AB - 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-1α 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.
KW - Alternative splicing
KW - Brown adipocyte
KW - PRDM16
KW - RBM4a
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U2 - 10.1016/j.bbamcr.2018.08.001
DO - 10.1016/j.bbamcr.2018.08.001
M3 - Article
AN - SCOPUS:85051460285
SN - 0167-4889
VL - 1865
SP - 1515
EP - 1525
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
IS - 11
ER -