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RNA剪接：一个分裂的共有序列揭示了两类主要的5'剪接位点。

RNA splicing: a split consensus reveals two major 5' splice site classes.

作者信息

Parker Matthew T, Fica Sebastian M, Simpson Gordon G

机构信息

Max Planck Institute for Plant Breeding Research , Cologne, Germany.

Department of Biochemistry, University of Oxford , Oxford, UK.

出版信息

Open Biol. 2025 Jan;15(1):240293. doi: 10.1098/rsob.240293. Epub 2025 Jan 15.

DOI:10.1098/rsob.240293
PMID:39809319
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11732430/
Abstract

The established consensus sequence for human 5' splice sites masks the presence of two major splice site classes defined by preferential base-pairing potentials with either U5 snRNA loop 1 or the U6 snRNA ACAGA box. The two 5' splice site classes are separable in genome sequences, sensitized by specific genotypes and associated with splicing complexity. The two classes reflect the commitment to 5' splice site usage occurring primarily during 5' splice site transfer to U6 snRNA. Separating the human 5' splice site consensus into its two major constituents can help us understand fundamental features of eukaryote genome architecture and splicing mechanisms and inform treatment design for diseases caused by genetic variation affecting splicing.

摘要

已确定的人类5'剪接位点共有序列掩盖了由与U5 snRNA环1或U6 snRNA ACAGA框的优先碱基配对潜力所定义的两种主要剪接位点类型的存在。这两种5'剪接位点类型在基因组序列中是可分离的，受特定基因型影响，并与剪接复杂性相关。这两种类型反映了主要在5'剪接位点转移到U6 snRNA期间对5'剪接位点使用的决定性作用。将人类5'剪接位点共有序列分为其两个主要组成部分，有助于我们理解真核生物基因组结构和剪接机制的基本特征，并为因影响剪接的基因变异而导致的疾病的治疗设计提供信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004b/11732430/85f4a4d1ee7e/rsob.240293.f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004b/11732430/29e59d7653bb/rsob.240293.fg001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004b/11732430/441cc0853bcb/rsob.240293.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004b/11732430/bbfeba839a06/rsob.240293.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004b/11732430/dee29661db3a/rsob.240293.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004b/11732430/2a2aa10cffa7/rsob.240293.f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004b/11732430/85f4a4d1ee7e/rsob.240293.f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004b/11732430/29e59d7653bb/rsob.240293.fg001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004b/11732430/441cc0853bcb/rsob.240293.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004b/11732430/bbfeba839a06/rsob.240293.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004b/11732430/dee29661db3a/rsob.240293.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004b/11732430/2a2aa10cffa7/rsob.240293.f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004b/11732430/85f4a4d1ee7e/rsob.240293.f005.jpg

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本文引用的文献

1
De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome.RNU4-2 snRNA 中的新生变异导致一种常见的神经发育综合征。
Nature. 2024 Aug;632(8026):832-840. doi: 10.1038/s41586-024-07773-7. Epub 2024 Jul 11.
2
Mutations in the U4 snRNA gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders.U4 snRNA 基因 RNU4-2 中的突变导致了最常见的单基因神经发育障碍之一。
Nat Med. 2024 Aug;30(8):2165-2169. doi: 10.1038/s41591-024-03085-5. Epub 2024 May 31.
3
U6 snRNA m6A modification is required for accurate and efficient splicing of C. elegans and human pre-mRNAs.
U6 snRNA m6A 修饰对于秀丽隐杆线虫和人类前体 mRNA 的准确和高效剪接是必需的。
Nucleic Acids Res. 2024 Aug 27;52(15):9139-9160. doi: 10.1093/nar/gkae447.
4
Structural insights into the cross-exon to cross-intron spliceosome switch.结构洞察跨外显子到跨内含子剪接体开关。
Nature. 2024 Jun;630(8018):1012-1019. doi: 10.1038/s41586-024-07458-1. Epub 2024 May 22.
5
Structural insights into human exon-defined spliceosome prior to activation.人类外显子定义的剪接体在激活前的结构见解。
Cell Res. 2024 Jun;34(6):428-439. doi: 10.1038/s41422-024-00949-w. Epub 2024 Apr 24.
6
Structural basis of U12-type intron engagement by the fully assembled human minor spliceosome.完全组装的人类小剪接体与U12型内含子结合的结构基础。
Science. 2024 Mar 15;383(6688):1245-1252. doi: 10.1126/science.adn7272. Epub 2024 Mar 14.
7
Random genetic drift sets an upper limit on mRNA splicing accuracy in metazoans.随机遗传漂变对后生动物mRNA剪接准确性设置了上限。
Elife. 2024 Mar 12;13:RP93629. doi: 10.7554/eLife.93629.
8
Cryo-EM analyses of dimerized spliceosomes provide new insights into the functions of B complex proteins.冷冻电镜分析二聚化剪接体为 B 复合物蛋白的功能提供了新的见解。
EMBO J. 2024 Mar;43(6):1065-1088. doi: 10.1038/s44318-024-00052-1. Epub 2024 Feb 21.
9
Structural insights into intron catalysis and dynamics during splicing.剪接过程中内含子催化和动力学的结构见解。
Nature. 2023 Dec;624(7992):682-688. doi: 10.1038/s41586-023-06746-6. Epub 2023 Nov 22.
10
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Elife. 2023 Oct 3;12:e91997. doi: 10.7554/eLife.91997.