Noisy splicing drives mRNA isoform diversity in human cells.
Noisy splicing drives mRNA isoform diversity in human cells.
复制标题
DOI：
10.1371/journal.pgen.1001236
复制
发表时间：
2010-12-09
期刊：
影响因子：
4.5
通讯作者：
Pritchard JK
中科院分区：
文献类型：
--
作者：
Pickrell JK;Pai AA;Gilad Y;Pritchard JK
虽然大多数多外显子人类基因显示出选择性剪接的一些证据，但尚不清楚观察到的剪接形式的哪一部分是功能相关的。在这项研究中，我们使用深度RNA测序和从头鉴定剪接点来研究人类细胞中选择性剪接的程度。我们证明了存在一个大类的低丰度异构体，包括约150,000以前未注释的剪接点在我们的数据。新发现的剪接位点几乎没有进化保守的证据，这表明大多数是由于错误的剪接位点的选择。我们发现，参与识别外显子的序列基序富集在不保守的剪接位点附近。我们估计内含子的平均剪接错误率约为0.7%，并表明高表达基因中的内含子剪接更准确，可能是由于它们的长度较短。这些结果暗示噪声剪接作为基因组进化的一个重要属性。大多数人类基因都被分割成片段，因此蛋白质编码部分（外显子）在基因组中被大量非编码DNA（内含子）分开，这些非编码DNA必须被转录和剪接以产生功能性转录物。剪接反应中的变异可以从同一基因产生多个转录本，但这些替代转录本中的许多转录本的功能是未知的。在这项研究中，我们表明，许多这些成绩单是由于剪接错误，而不是保存在进化的时间。我们估计，在剪接的内含子的错误率约为0.7%，并证明有两种主要类型的剪接错误：错误的识别外显子和错误的剪接位点的精确选择。这些结果提出了一种可能性，即不同物种间选择性剪接水平的变化可能部分是剪接错误率的变化。
While the majority of multiexonic human genes show some evidence of alternative splicing, it is unclear what fraction of observed splice forms is functionally relevant. In this study, we examine the extent of alternative splicing in human cells using deep RNA sequencing and de novo identification of splice junctions. We demonstrate the existence of a large class of low abundance isoforms, encompassing approximately 150,000 previously unannotated splice junctions in our data. Newly-identified splice sites show little evidence of evolutionary conservation, suggesting that the majority are due to erroneous splice site choice. We show that sequence motifs involved in the recognition of exons are enriched in the vicinity of unconserved splice sites. We estimate that the average intron has a splicing error rate of approximately 0.7% and show that introns in highly expressed genes are spliced more accurately, likely due to their shorter length. These results implicate noisy splicing as an important property of genome evolution. Most human genes are split into pieces, such that the protein-coding parts (exons) are separated in the genome by large tracts of non-coding DNA (introns) that must be transcribed and spliced out to create a functional transcript. Variation in splicing reactions can create multiple transcripts from the same gene, yet the function for many of these alternative transcripts is unknown. In this study, we show that many of these transcripts are due to splicing errors which are not preserved over evolutionary time. We estimate that the error rate in the splicing of an intron is about 0.7% and demonstrate that there are two major types of splicing error: errors in the recognition of exons and errors in the precise choice of splice site. These results raise the possibility that variation in levels of alternative splicing across species may in part be to variation in splicing error rate.
登录
查看更多内容
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：
7
作者：
Fraser, Hunter B.;Xie, Xiaohui
通讯作者：
Xie, Xiaohui
DOI：
10.1073/pnas.0506139102
发表时间：
2005-09-06
影响因子：
11.1
作者：
Baek, D;Green, P
通讯作者：
Green, P
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
30.8
作者：
Kolasinska-Zwierz P;Down T;Latorre I;Liu T;Liu XS;Ahringer J
通讯作者：
Ahringer J