title: RBM4a-regulated splicing cascade modulates the differentiation and metabolic activities of brown adipocytes.
abstract: RNA-binding motif protein 4a (RBM4a) reportedly reprograms splicing profiles of the insulin receptor (IR) and myocyte enhancer factor 2C (MEF2C) genes, facilitating the differentiation of brown adipocytes. Using an RNA-sequencing analysis, we first compared the gene expressing profiles between wild-type and RBM4a(-/-) brown adipocytes. The ablation of RBM4a led to increases in the PTBP1, PTBP2 (nPTB), and Nova1 proteins, whereas elevated RBM4a reduced the expression of PTBP1 and PTBP2 proteins in brown adipocytes through an alternative splicing-coupled nonsense-mediated decay mechanism. Subsequently, RBM4a indirectly shortened the half-life of the Nova1 transcript which was comparatively stable in the presence of PTBP2. RBM4a diminished the influence of PTBP2 in adipogenic development by reprogramming the splicing profiles of the FGFR2 and PKM genes. These results constitute a mechanistic understanding of the RBM4a-modulated splicing cascade during the brown adipogenesis.
authors: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors: Jung-Chun
authors: JC
authors: Lin
authors: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors: Yi-Han
authors: YH
authors: Lu
authors: Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan.
authors: Yun-Ru
authors: YR
authors: Liu
authors: School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors: Ying-Ju
authors: YJ
authors: Lin
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D000090682:Neuro-Oncological Ventral Antigen; D038941:Polypyrimidine Tract-Binding Protein / Q000096:biosynthesis / Q000235:genetics; D012326:RNA Splicing / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009419:Nerve Tissue Proteins; D000090682:Neuro-Oncological Ventral Antigen; C000608219:Nova1 protein, mouse; C573992:Ptbp1 protein, mouse; C429773:Ptbp2 protein, mouse; D016601:RNA-Binding Proteins; D038941:Polypyrimidine Tract-Binding Protein