Tissue Usage Preference and Intrinsically Disordered Region Remodeling of Alternative Splicing Derived Proteoforms in the Heart.
Tissue Usage Preference and Intrinsically Disordered Region Remodeling of Alternative Splicing Derived Proteoforms in the Heart.
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心脏中选择性剪接衍生蛋白质形式的组织使用偏好和本质无序区域重塑。
DOI：
10.1101/2023.10.08.561375
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Lam,MaggiePY
中科院分区：
文献类型：
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作者：
Pandi,Boomathi;Brenman,Stella;Black,Alexander;Ng,DominicCM;Lau,Edward;Lam,MaggiePY
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。心房和心室中存在216种非典型亚型的证据，包括SwissProt上未记录的52种亚型，并使用RNA测序衍生数据库回收。在非典型亚型中，29种显示出基于组织使用的统计学显著偏好的调节迹象，包括心室富集的张力蛋白-1（TNS 1）和心房富集的PDZ和LIM结构域3（PDLIM 3）亚型2（PDLIM 3 -2/ALP-H）。在替代同种型和典型同种型之间不同的检查的变体区域高度富集有固有无序区域。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。这里的分析提供了进一步的证据的概念，选择性剪接多样化的蛋白质组通过重新布线的内在无序的区域，这是越来越多地认识到发挥重要作用，从蛋白质序列的生物功能的产生。
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.