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A potential mechanism underlying U1 snRNP inhibition of the cleavage step of mRNA 3' processing.
Biochemical and Biophysical Research Communications ( IF 2.5 ) Pub Date : 2020-08-01 , DOI: 10.1016/j.bbrc.2020.06.092
Yanhui Deng 1 , Junjie Shi 1 , Yi Ran 1 , Andy Peng Xiang 1 , Chengguo Yao 2
Affiliation  

It is well established that U1 snRNP inhibits the cleavage of cryptic polyadenylation site (PAS) within introns, thereby facilitating full-length mRNA transcription for numerous genes in vertebrate cells, yet the underlying mechanism remains poorly understood. Here, by using a model PAS of wdr26 mRNA, we show that U1 snRNP predominantly interferes with the association of PAS with a core 3′ processing factor CstF64, which can promote the cleavage step of mRNA 3′ processing. Furthermore, we provide evidence that U1A, a component of U1 snRNP, might directly interfere with CstF64 binding on PAS through its RNA binding capacity. Consistently, U1A could potentially associate with U1-suppressed intronic PASs at the transcriptome level in human cells, showing a binding peak ∼50 nt downstream of the cleavage site, as revealed by U1A iCLIP-seq (individual-nucleotide resolution UV crosslinking and immunoprecipitation coupled with RNA sequencing) analysis. Together, our data suggest a molecular mechanism underlying U1 snRNP inhibition of the cleavage step of mRNA 3′ processing. More generally, we argue that U1 snRNP might inhibit the usage of cryptic PASs through disturbing the recruitment of core 3’ processing factors.



中文翻译:

U1 snRNP抑制mRNA 3'加工的裂解步骤的潜在机制。

公认的是,U1 snRNP抑制内含子内隐性多腺苷酸化位点(PAS)的切割,从而促进脊椎动物细胞中许多基因的全长mRNA转录,但其潜在机制仍知之甚少。在这里,通过使用wdr2的模型PAS在图6的mRNA中,我们显示U1 snRNP主要干扰PAS与核心3'加工因子CstF64的缔合,其可以促进mRNA 3'加工的切割步骤。此外,我们提供的证据表明,U1A(U1 snRNP的一个组成部分)可能通过其RNA结合能力直接干扰PAS上的CstF64结合。一致地,U1A可能在人类细胞的转录组水平上与U1抑制的内含子PASs缔合,在裂解位点下游显示一个约50 nt的结合峰,如U1A iCLIP-seq(个体核苷酸分辨率UV交联和免疫沉淀偶联)所揭示。 RNA测序)分析。在一起,我们的数据表明潜在的分子机制的U1 snRNP抑制mRNA 3'加工的切割步骤。更普遍,

更新日期:2020-08-01
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