Alternative splicing at GYNNGY 5' splice sites: more noise, less regulation.
Alternative splicing at GYNNGY 5' splice sites: more noise, less regulation.
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DOI：
10.1093/nar/gku1253
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发表时间：
2014-12-16
影响因子：
14.9
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Wang M;Zhang P;Shu Y;Yuan F;Zhang Y;Zhou Y;Jiang M;Zhu Y;Hu L;Kong X;Zhang Z
许多真核基因是选择性剪接的。近年来，深度转录组测序使选择性剪接基因的比例急剧上升，超过95%的人类多外显子基因是选择性剪接的。一个基本的问题是：所有这些选择性剪接（AS）事件都有功能吗？为了探讨这个问题，我们研究了最常见的5′剪接位点-GYNNGY（Y = C/T），其中两个GY都可以作为剪接位点。全局分析表明，剪接噪声（由于剪接过程的随机性）可以导致AS在GYNNGY，证明了较高的AS频率在非编码区比在编码区，在非保守的基因比在保守的基因和低表达的基因比在高表达的基因。然而，人类中约20%的AS GYNNGY和小鼠中约3%的AS GYNNGY表现出组织依赖性调节。与功能性一致，受调节的GYNNGY比未受调节的GYNNGY更保守。受调控的GYNNGY具有独特的序列特征，这可能会导致调控。特别地，每个受调节的GYNNGY包含两个比未受调节的GYNNGY彼此更相似的剪接位点，并且具有更保守的下游侧翼内含子。有趣的是，大多数受调控的GYNNGY可能通过与无义介导的mRNA衰变偶联来调节基因表达，而不是编码不同的蛋白质。总之，GYNNGY 5′剪接位点的AS主要是剪接噪声，其次是一种调节方式。
Numerous eukaryotic genes are alternatively spliced. Recently, deep transcriptome sequencing has skyrocketed proportion of alternatively spliced genes; over 95% human multi-exon genes are alternatively spliced. One fundamental question is: are all these alternative splicing (AS) events functional? To look into this issue, we studied the most common form of alternative 5′ splice sites—GYNNGYs (Y = C/T), where both GYs can function as splice sites. Global analyses suggest that splicing noise (due to stochasticity of splicing process) can cause AS at GYNNGYs, evidenced by higher AS frequency in non-coding than in coding regions, in non-conserved than in conserved genes and in lowly expressed than in highly expressed genes. However, ∼20% AS GYNNGYs in humans and ∼3% in mice exhibit tissue-dependent regulation. Consistent with being functional, regulated GYNNGYs are more conserved than unregulated ones. And regulated GYNNGYs have distinctive sequence features which may confer regulation. Particularly, each regulated GYNNGY comprises two splice sites more resembling each other than unregulated GYNNGYs, and has more conserved downstream flanking intron. Intriguingly, most regulated GYNNGYs may tune gene expression through coupling with nonsense-mediated mRNA decay, rather than encode different proteins. In summary, AS at GYNNGY 5′ splice sites is primarily splicing noise, and secondarily a way of regulation.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.5
作者：
Chern, Tzu-Ming;van Nimwegen, Erik;Kai, Chikatoshi;Kawai, Jun;Carninci, Piero;Hayashizaki, Yoshihide;Zavolan, Mihaela
通讯作者：
Zavolan, Mihaela
影响因子：
14.9
作者：
Flicek P;Ahmed I;Amode MR;Barrell D;Beal K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fairley S;Fitzgerald S;Gil L;García-Girón C;Gordon L;Hourlier T;Hunt S;Juettemann T;Kähäri AK;Keenan S;Komorowska M;Kulesha E;Longden I;Maurel T;McLaren WM;Muffato M;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ritchie GR;Ruffier M;Schuster M;Sheppard D;Sobral D;Taylor K;Thormann A;Trevanion S;White S;Wilder SP;Aken BL;Birney E;Cunningham F;Dunham I;Harrow J;Herrero J;Hubbard TJ;Johnson N;Kinsella R;Parker A;Spudich G;Yates A;Zadissa A;Searle SM
通讯作者：
Searle SM
DOI：
10.1073/pnas.1207846109
发表时间：
2012-09-11
影响因子：
11.1
作者：
Lee, Sooncheol;Liu, Botao;Qian, Shu-Bing
通讯作者：
Qian, Shu-Bing
人类大脑发育和衰老过程中广泛的剪接变化
影响因子：
9.9
作者：
Mazin, Pavel;Xiong, Jieyi;Khaitovich, Philipp
通讯作者：
Khaitovich, Philipp