PDF(Pubmed)
Abstract：
A computational analysis of mass spectrometry data was performed to uncover alternative splicing derived protein variants across chambers of the human heart. Evidence for 216 non-canonical isoforms was apparent in the atrium and the ventricle, including 52 isoforms not documented on SwissProt and recovered using an RNA sequencing derived database. Among non-canonical isoforms, 29 show signs of regulation based on statistically significant preferences in tissue usage, including a ventricular enriched protein isoform of tensin-1 (TNS1) and an atrium-enriched PDZ and LIM Domain 3 (PDLIM3) isoform 2 (PDLIM3-2/ALP-H). Examined variant regions that differ between alternative and canonical isoforms are highly enriched with intrinsically disordered regions. Moreover, over two-thirds of such regions are predicted to function in protein binding and RNA binding. The analysis here lends further credence to the notion that alternative splicing diversifies the proteome by rewiring intrinsically disordered regions, which are increasingly recognized to play important roles in the generation of biological function from protein sequences.
摘要：
进行质谱数据的计算分析以揭示跨人类心脏腔室的可变剪接衍生的蛋白质变体。在心房和心室中有216种非典型同工型的证据，包括未在SwissProt上记录的52种同工型，并使用RNA测序衍生数据库回收。在非规范同工型中，29显示了基于组织使用的统计显着偏好的调节迹象，包括心室富含张力蛋白1（TNS1）和心房富含PDZ和LIM结构域3（PDLIM3）亚型2（PDLIM3-2/ALP-H）。在替代和规范同种型之间不同的已检查变体区域高度富含固有的无序区域。此外，预计超过三分之二的此类区域在蛋白质结合和RNA结合中起作用。这里的分析进一步证明了这样一种观点，即选择性剪接通过重新布线内在无序的区域来使蛋白质组多样化，越来越多的人认识到在从蛋白质序列产生生物学功能中发挥重要作用。
