Polypyrimidine tract binding proteins PTBP1 and PTBP2 interact with distinct proteins under splicing conditions.
Polypyrimidine tract binding proteins PTBP1 and PTBP2 interact with distinct proteins under splicing conditions.
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DOI：
10.1371/journal.pone.0263287
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Keppetipola NM
中科院分区：
文献类型：
--
作者：
Pina JM;Hernandez LA;Keppetipola NM
RNA 结合蛋白在调节选择性前 mRNA 剪接以及细胞基因表达方面发挥着重要作用。多聚嘧啶束结合蛋白 PTBP1 和 PTBP2 是旁系同源 RNA 结合蛋白，在神经元分化和成熟过程中发挥关键作用；神经元发育过程中 PTBP 蛋白浓度的变化直接导致许多转录本的剪接变化，这些转录本编码对神经元分化至关重要的蛋白质。这两种相关蛋白如何调节不同组的神经元外显子尚不清楚。 PTBP1 和 PTBP2 的不同剪接活性可以在体外剪接系统中通过 c-src 前 mRNA 的差异调节 N1 外显子来重现。在这里，我们在这些体外剪接条件下进行了实验，以鉴定 PTBP1 和 PTBP2 相互作用的伴侣蛋白。我们的结果强调，两种 PTBP 都与参与染色质重塑和转录调控的蛋白质相互作用。我们的数据表明，PTBP1 与许多参与 mRNA 加工（包括剪接调节）的蛋白质相互作用，而 PTBP2 则不然。我们的结果还强调了酶可以作为潜在的“书写器”和“擦除器”，为 PTB 蛋白添加化学修饰。总体而言，我们的研究强调了剪接条件下 PTBP 蛋白之间蛋白质-蛋白质相互作用的重要差异，并支持翻译后修饰在决定其不同剪接活性中的作用。
RNA binding proteins play an important role in regulating alternative pre-mRNA splicing and in turn cellular gene expression. Polypyrimidine tract binding proteins, PTBP1 and PTBP2, are paralogous RNA binding proteins that play a critical role in the process of neuronal differentiation and maturation; changes in the concentration of PTBP proteins during neuronal development direct splicing changes in many transcripts that code for proteins critical for neuronal differentiation. How the two related proteins regulate different sets of neuronal exons is unclear. The distinct splicing activities of PTBP1 and PTBP2 can be recapitulated in an in vitro splicing system with the differentially regulated N1 exon of the c-src pre-mRNA. Here, we conducted experiments under these in vitro splicing conditions to identify PTBP1 and PTBP2 interacting partner proteins. Our results highlight that both PTBPs interact with proteins that participate in chromatin remodeling and transcription regulation. Our data reveal that PTBP1 interacts with many proteins involved in mRNA processing including splicing regulation while PTBP2 does not. Our results also highlight enzymes that can serve as potential “writers” and “erasers” in adding chemical modifications to the PTB proteins. Overall, our study highlights important differences in protein-protein interactions between the PTBP proteins under splicing conditions and supports a role for post-translational modifications in dictating their distinct splicing activities.
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