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Altered expressions and splicing profiles of Acin1 transcripts differentially modulate brown adipogenesis through an alternative splicing mechanism.
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms ( IF 2.6 ) Pub Date : 2020-07-03 , DOI: 10.1016/j.bbagrm.2020.194601
Ying-Chin Lin , Yi-Han Lu , Yuan-Chii Lee , Ching-Sheng Hung , Jung-Chun Lin

Apoptotic chromatin condensation inducer in the nucleus (also referred as Acin1) was first characterized as an RNA-binding protein involved in apoptosis. In later reports, Acin1 was identified as an auxiliary component of the exon junction complex (EJC) which is assembled throughout pre-messenger RNA splicing. In this study, results of whole-transcriptome analyses revealed reduced expressions and reprogrammed splicing profiles of Acin1 transcripts throughout development of brown adipose tissues (BATs) that execute non-shivering thermogenesis in small rodents and infants by consuming lipids. Depletion of endogenous Acin1 isoforms led to activation of brown adipogenic signatures in mouse C3H10T1/2 fibroblasts. Nevertheless, overexpressions of the Acin1-L or Acin1-S isoform exerted discriminative influences on brown adipogenesis and reprogramming of the expression of serine/arginine-rich splicing factor 3 (SRSF3) through an alternative splicing-coupled nonsense-mediated decay mechanism in a sequence-specific manner. Moreover, the Acin1-SRSF3 axis constitutes a regulatory pathway that participates in the brown adipocyte-related splicing network. Taken together, the interplay between accessory EJC components and splicing regulators constitutes an emerging mechanism for differentially manipulating the activity of brown adipogenesis via alternative splicing network.



中文翻译:

Acin1转录物的改变的表达和剪接图谱通过另一种剪接机制差异性调节褐色脂肪形成。

核中的凋亡染色质凝结诱导剂(也称为Acin1)首先被表征为参与凋亡的RNA结合蛋白。在以后的报告中,Acin1被确定为外显子连接复合物(EJC)的辅助成分,该复合物在信使前RNA剪接过程中一直组装在一起。在这项研究中,全转录组分析的结果显示Acin1的表达减少和剪接图谱被重新编程棕色脂肪组织(BATs)整个发育过程中的转录本,它们通过消耗脂质在小型啮齿动物和婴儿中执行无颤抖的生热作用。内源性Acin1亚型的耗竭导致小鼠C3H10T1 / 2成纤维细胞中棕色脂肪形成信号的激活。然而,Acin1-L或Acin1-S亚型的过表达对棕色脂肪形成和丝氨酸/精氨酸丰富的剪接因子3(SRSF3)的表达通过序列中的另一种剪接偶联的无义介导的衰变机制产生了歧视性影响。特定的方式。此外,Acin1-SRSF3轴构成参与棕色脂肪细胞相关的剪接网络的调节途径。在一起通过替代的拼接网络。

更新日期:2020-07-07
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