U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3' end processing core factors.
U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3' end processing core factors.
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U1 snRNP 蛋白通过直接与 3â2 末端加工核心因子相互作用来促进近端选择性多聚腺苷酸化位点
DOI：
10.1093/jmcb/mjac054
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发表时间：
2022-12-26
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
在真核细胞中，选择性剪接和选择性聚腺苷酸化（阿帕）在基因调控网络中起着重要作用。U1小核糖核蛋白颗粒（U1 snRNP）是剪接体的主要成分，U1 snRNP复合物通过与3′端加工因子的交联作用抑制近端阿帕位点。然而，在这里，我们表明，敲低和SNRPA，SNRPC，SNRNP70和SNRPD2，U1 snRNP蛋白的过表达，促进近端阿帕位点在转录组水平的使用。SNRNP70可以驱动PABPN1从液滴到聚集体的相变，这可能会降低PABPN1对近端阿帕位点的抑制作用。此外，SNRNP70还可以通过募集CPSF 6来促进APA近端位点的表达，提示CPSF 6对阿帕的作用与其他RNA结合蛋白有关，并具有细胞环境依赖性。结果表明，与U1 snRNP复合物相反，U1 snRNP复合物中的游离蛋白通过与3′端加工机制的相互作用，可以促进近端阿帕位点的活性。
In eukaryotic cells, both alternative splicing and alternative polyadenylation (APA) play essential roles in the gene regulation network. U1 small ribonucleoprotein particle (U1 snRNP) is a major component of spliceosome, and U1 snRNP complex can suppress proximal APA sites through crosstalking with 3′ end processing factors. However, here we show that both knockdown and overexpression of SNRPA, SNRPC, SNRNP70, and SNRPD2, the U1 snRNP proteins, promote the usage of proximal APA sites at the transcriptome level. SNRNP70 can drive the phase transition of PABPN1 from droplet to aggregate, which may reduce the repressive effects of PABPN1 on the proximal APA sites. Additionally, SNRNP70 can also promote the proximal APA sites by recruiting CPSF6, suggesting that the function of CPSF6 on APA is related with other RNA-binding proteins and cell context-dependent. Consequently, these results reveal that, on the contrary to U1 snRNP complex, the free proteins of U1 snRNP complex can promote proximal APA sites through the interaction with 3′ end processing machinery.
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