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鼠核 RNAi 缺陷 2 促进弱 5' 剪接位点的剪接。

Mouse nuclear RNAi-defective 2 promotes splicing of weak 5' splice sites.

机构信息

Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.

Swiss Institute of Bioinformatics, 4058 Basel, Switzerland.

出版信息

RNA. 2023 Aug;29(8):1140-1165. doi: 10.1261/rna.079465.122. Epub 2023 May 3.

DOI:10.1261/rna.079465.122
PMID:37137667
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10351895/
Abstract

Removal of introns during pre-mRNA splicing, which is central to gene expression, initiates by base pairing of U1 snRNA with a 5' splice site (5'SS). In mammals, many introns contain weak 5'SSs that are not efficiently recognized by the canonical U1 snRNP, suggesting alternative mechanisms exist. Here, we develop a cross-linking immunoprecipitation coupled to a high-throughput sequencing method, BCLIP-seq, to identify NRDE2 (nuclear RNAi-defective 2), and CCDC174 (coiled-coil domain-containing 174) as novel RNA-binding proteins in mouse ES cells that associate with U1 snRNA and 5'SSs. Both proteins bind directly to U1 snRNA independently of canonical U1 snRNP-specific proteins, and they are required for the selection and effective processing of weak 5'SSs. Our results reveal that mammalian cells use noncanonical splicing factors bound directly to U1 snRNA to effectively select suboptimal 5'SS sequences in hundreds of genes, promoting proper splice site choice, and accurate pre-mRNA splicing.

摘要

在基因表达中至关重要的前体 mRNA 剪接过程中，内含子的去除是通过 U1 snRNA 与 5' 剪接位点（5'SS）的碱基配对起始的。在哺乳动物中，许多内含子含有较弱的 5'SS，这些 5'SS 不能被经典的 U1 snRNP 有效识别，这表明存在替代机制。在这里，我们开发了一种交联免疫沉淀结合高通量测序方法 BCLIP-seq，以鉴定 NRDE2（核 RNAi 缺陷 2）和 CCDC174（卷曲螺旋结构域包含 174）作为与 U1 snRNA 和 5'SS 相关的新型 RNA 结合蛋白在小鼠 ES 细胞中。这两种蛋白均可独立于经典的 U1 snRNP 特异性蛋白直接与 U1 snRNA 结合，并且它们是弱 5'SS 选择和有效加工所必需的。我们的研究结果揭示了哺乳动物细胞使用直接结合 U1 snRNA 的非经典剪接因子，有效地选择数百个基因中次优的 5'SS 序列，促进适当的剪接位点选择和准确的前体 mRNA 剪接。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/0af0b1f00a8b/1140f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/aaf105fbbca0/1140f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/d403ada1d4a5/1140f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/8e5c0c76fac2/1140f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/5c2965cf8222/1140f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/3d47e2266251/1140f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/27a9ed292cea/1140f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/0af0b1f00a8b/1140f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/aaf105fbbca0/1140f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/d403ada1d4a5/1140f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/8e5c0c76fac2/1140f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/5c2965cf8222/1140f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/3d47e2266251/1140f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/27a9ed292cea/1140f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc9/10351895/0af0b1f00a8b/1140f07.jpg

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2
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F1000Res. 2020 Apr 28;9. doi: 10.12688/f1000research.23297.2. eCollection 2020.
3
Mammalian RNA Decay Pathways Are Highly Specialized and Widely Linked to Translation.哺乳动物的 RNA 降解途径高度专业化，并广泛与翻译相关联。
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4
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Mol Cell. 2020 Mar 5;77(5):985-998.e8. doi: 10.1016/j.molcel.2019.11.017. Epub 2019 Dec 12.
5
RNA Splicing by the Spliceosome.剪接体的 RNA 剪接。
Annu Rev Biochem. 2020 Jun 20;89:359-388. doi: 10.1146/annurev-biochem-091719-064225. Epub 2019 Dec 3.
6
Alternative Splicing Regulatory Networks: Functions, Mechanisms, and Evolution.可变剪接调控网络：功能、机制与演化。
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7
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8
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9
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