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必需的前体mRNA剪接因子U2AF65识别聚嘧啶序列的结构基础。

Structural basis for polypyrimidine tract recognition by the essential pre-mRNA splicing factor U2AF65.

作者信息

Sickmier E Allen, Frato Katherine E, Shen Haihong, Paranawithana Shanthi R, Green Michael R, Kielkopf Clara L

机构信息

Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.

出版信息

Mol Cell. 2006 Jul 7;23(1):49-59. doi: 10.1016/j.molcel.2006.05.025.

DOI:10.1016/j.molcel.2006.05.025
PMID:16818232
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2043114/
Abstract

The essential pre-mRNA splicing factor, U2AF(65), guides the early stages of splice site choice by recognizing a polypyrimidine (Py) tract consensus sequence near the 3' splice site. Since Py tracts are relatively poorly conserved in higher eukaryotes, U2AF(65) is faced with the problem of specifying uridine-rich sequences, yet tolerating a variety of nucleotide substitutions found in natural Py tracts. To better understand these apparently contradictory RNA binding characteristics, the X-ray structure of the U2AF(65) RNA binding domain bound to a Py tract composed of seven uridines has been determined at 2.5 A resolution. Specific hydrogen bonds between U2AF(65) and the uracil bases provide an explanation for polyuridine recognition. Flexible side chains and bound water molecules form the majority of the base contacts and potentially could rearrange when the U2AF(65) structure adapts to different Py tract sequences. The energetic importance of conserved residues for Py tract binding is established by analysis of site-directed mutant U2AF(65) proteins using surface plasmon resonance.

摘要

基本的前体mRNA剪接因子U2AF(65)，通过识别3'剪接位点附近的多嘧啶（Py）序列共有序列，指导剪接位点选择的早期阶段。由于Py序列在高等真核生物中相对保守性较差，U2AF(65)面临着确定富含尿苷的序列的问题，同时还要容忍天然Py序列中发现的各种核苷酸替换。为了更好地理解这些明显相互矛盾的RNA结合特性，已在2.5埃分辨率下确定了与由七个尿苷组成的Py序列结合的U2AF(65)RNA结合结构域的X射线结构。U2AF(65)与尿嘧啶碱基之间的特定氢键为多尿苷识别提供了解释。柔性侧链和结合的水分子构成了大部分碱基接触，并且当U2AF(65)结构适应不同的Py序列时可能会重新排列。通过使用表面等离子体共振分析定点突变的U2AF(65)蛋白，确定了保守残基对Py序列结合的能量重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c30/2043114/8196a8eef8b6/nihms26345f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c30/2043114/a30dc475ff26/nihms26345f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c30/2043114/fcda9ae03d5b/nihms26345f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c30/2043114/2f001bbc0ad7/nihms26345f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c30/2043114/7c33d5681f06/nihms26345f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c30/2043114/8196a8eef8b6/nihms26345f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c30/2043114/a30dc475ff26/nihms26345f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c30/2043114/fcda9ae03d5b/nihms26345f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c30/2043114/2f001bbc0ad7/nihms26345f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c30/2043114/7c33d5681f06/nihms26345f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c30/2043114/8196a8eef8b6/nihms26345f5.jpg

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1
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2
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Methods Enzymol. 1997;277:505-24. doi: 10.1016/s0076-6879(97)77028-9.
3
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DDX39B 的募集效率低下会阻碍内含子上的前剪接体组装。
RNA. 2024 Jun 17;30(7):824-838. doi: 10.1261/rna.079933.123.
4
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Nat Commun. 2023 Sep 4;14(1):5366. doi: 10.1038/s41467-023-40254-5.
5
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RNA. 2023 Nov;29(11):1725-1737. doi: 10.1261/rna.079695.123. Epub 2023 Aug 11.
6
Purifying selection against spurious splicing signals contributes to the base composition evolution of the polypyrimidine tract.净化选择可消除假剪接信号，从而导致多嘧啶区碱基组成的进化。
J Evol Biol. 2023 Sep;36(9):1295-1312. doi: 10.1111/jeb.14205. Epub 2023 Aug 11.
7
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8
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9
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10
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Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 May 1;62(Pt 5):457-9. doi: 10.1107/S1744309106012504. Epub 2006 Apr 12.
4
Structure of PTB bound to RNA: specific binding and implications for splicing regulation.与RNA结合的PTB结构：特异性结合及其对剪接调控的影响
Science. 2005 Sep 23;309(5743):2054-7. doi: 10.1126/science.1114066.
5
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Mol Cell. 2005 Aug 19;19(4):485-96. doi: 10.1016/j.molcel.2005.07.014.
6
The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression.RNA识别基序，一种调控转录后基因表达的可塑性RNA结合平台。
FEBS J. 2005 May;272(9):2118-31. doi: 10.1111/j.1742-4658.2005.04653.x.
7
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10
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