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U5 snRNA 内部环 1 是 Brr2、Snu114 和 Prp8 蛋白在 U5 snRNP 组装过程中结合的平台。

The U5 snRNA internal loop 1 is a platform for Brr2, Snu114 and Prp8 protein binding during U5 snRNP assembly.

机构信息

Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, United Kingdom.

出版信息

J Cell Biochem. 2013 Dec;114(12):2770-84. doi: 10.1002/jcb.24625.

DOI:10.1002/jcb.24625
PMID:23857713
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4065371/
Abstract

The U5 small nuclear ribonucleoprotein particle (snRNP) forms the heart of the spliceosome which is required for intron removal from pre-mRNA. The proteins Prp8, Snu114 and Brr2 all assemble with the U5 small nuclear RNA (snRNA) to produce the U5 snRNP. Successful assembly of the U5 snRNP, then incorporation of this snRNP into the U4/U6.U5 tri-snRNP and the spliceosome, is essential for producing an active spliceosome. We have investigated the requirements for Prp8, Snu114 and Brr2 association with the U5 snRNA to form the U5 snRNP in yeast. Mutations were constructed in the highly conserved loop 1 and internal loop 1 (IL1) of the U5 snRNA and their function assessed in vivo. The influence of these U5 mutations on association of Prp8, Snu114 and Brr2 with the U5 snRNA were then determined. U5 snRNA loop 1 and both sides of IL1 in U5 were important for association of Prp8, Snu114 and Brr2 with the U5 snRNA. Mutations in the 3' side of U5 IL1 resulted in the greatest reduction of Prp8, Snu114 and Brr2 association with the U5 snRNA. Genetic screening of brr2 and U5 snRNA mutants revealed synthetic lethal interactions between alleles in Brr2 and the 3' side of U5 snRNA IL1 which reflects reduced association between Brr2 and U5 IL1. We propose that the U5 snRNA IL1 is a platform for protein binding and is required for Prp8, Brr2 and Snu114 association with the U5 snRNA to form the U5 snRNP.

摘要

U5 小核核糖核蛋白颗粒（snRNP）是剪接体的核心，剪接体是从前体 mRNA 中去除内含子所必需的。Prp8、Snu114 和 Brr2 蛋白都与 U5 小核 RNA（snRNA）组装形成 U5 snRNP。U5 snRNP 的成功组装，然后将该 snRNP 掺入 U4/U6.U5 三 snRNP 和剪接体中，对于产生活性剪接体是必不可少的。我们已经研究了 Prp8、Snu114 和 Brr2 与 U5 snRNA 结合形成 U5 snRNP 的要求在酵母中。构建了 U5 snRNA 高度保守的环 1 和内部环 1（IL1）中的突变，并在体内评估了它们的功能。然后确定了这些 U5 突变对 Prp8、Snu114 和 Brr2 与 U5 snRNA 结合的影响。U5 snRNA 环 1 和 U5 中的两个 IL1 侧对 Prp8、Snu114 和 Brr2 与 U5 snRNA 的结合很重要。U5 IL1 的 3'侧突变导致 Prp8、Snu114 和 Brr2 与 U5 snRNA 结合的减少最大。brr2 和 U5 snRNA 突变体的遗传筛选揭示了 Brr2 等位基因和 U5 snRNA IL1 的 3'侧之间的合成致死相互作用，这反映了 Brr2 和 U5 IL1 之间的结合减少。我们提出 U5 snRNA IL1 是蛋白质结合的平台，是 Prp8、Brr2 和 Snu114 与 U5 snRNA 结合形成 U5 snRNP 所必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/6141ebeb742d/jcb0114-2770-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/64733018d589/jcb0114-2770-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/12af058cfcca/jcb0114-2770-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/df8e1bb85b1e/jcb0114-2770-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/19ab35db1fc1/jcb0114-2770-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/1dafb14bd581/jcb0114-2770-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/39a78eeaa3e4/jcb0114-2770-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/60485a558928/jcb0114-2770-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/6141ebeb742d/jcb0114-2770-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/64733018d589/jcb0114-2770-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/12af058cfcca/jcb0114-2770-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/df8e1bb85b1e/jcb0114-2770-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/19ab35db1fc1/jcb0114-2770-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/1dafb14bd581/jcb0114-2770-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/39a78eeaa3e4/jcb0114-2770-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/60485a558928/jcb0114-2770-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/4065371/6141ebeb742d/jcb0114-2770-f8.jpg

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