Quantification of stochastic noise of splicing and polyadenylation in Entamoeba histolytica.

Quantification of stochastic noise of splicing and polyadenylation in Entamoeba histolytica.
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DOI:
10.1093/nar/gks1271
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发表时间:
2013-02-01
影响因子:
14.9
通讯作者:
Guillen N
Guillen N
中科院分区:
生物学2区
文献类型:
--
作者:
Hon CC;Weber C;Sismeiro O;Proux C;Koutero M;Deloger M;Das S;Agrahari M;Dillies MA;Jagla B;Coppee JY;Bhattacharya A;Guillen N

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在真核信使 RNA 中普遍观察到选择性剪接和聚腺苷酸化。这些替代亚型可能是生理调节的结果,也可能是 RNA 加工的随机噪声的结果。为了量化剪接和聚腺苷酸化中随机噪声的程度,我们使用 RNA-Seq 分析了溶组织内阿米巴中剪接和聚腺苷酸化位点的替代使用。首先,我们鉴定了大量很少剪接的选择性连接点,然后表明这些选择性剪接事件的发生与剪接位点序列、组成型剪接事件的发生和信使RNA丰度相关。我们的结果表明,这些替代拼接事件中的大多数可能是拼接机器的随机误差,并且我们估计了相应的错误率。其次,我们观察到多腺苷酸化裂解位点广泛的微观异质性,并且这种微观异质性的程度与组成型裂解事件的发生相关,表明大多数这种微观异质性可能是随机的。总体而言,我们只观察到一小部分选择性剪接和多腺苷酸化亚型,它们不可能完全是随机的,这意味着溶组织内阿米巴中选择性剪接和多腺苷酸化的功能相关性是有限的。最后,我们修改了基因模型,并在 AmoebaDB 中注释了其 3'UTR,为社区提供了宝贵的资源。
Alternative splicing and polyadenylation were observed pervasively in eukaryotic messenger RNAs. These alternative isoforms could either be consequences of physiological regulation or stochastic noise of RNA processing. To quantify the extent of stochastic noise in splicing and polyadenylation, we analyzed the alternative usage of splicing and polyadenylation sites in Entamoeba histolytica using RNA-Seq. First, we identified a large number of rarely spliced alternative junctions and then showed that the occurrence of these alternative splicing events is correlated with splicing site sequence, occurrence of constitutive splicing events and messenger RNA abundance. Our results implied the majority of these alternative splicing events are likely to be stochastic error of splicing machineries, and we estimated the corresponding error rates. Second, we observed extensive microheterogeneity of polyadenylation cleavage sites, and the extent of such microheterogeneity is correlated with the occurrence of constitutive cleavage events, suggesting most of such microheterogeneity is likely to be stochastic. Overall, we only observed a small fraction of alternative splicing and polyadenylation isoforms that are unlikely to be solely stochastic, implying the functional relevance of alternative splicing and polyadenylation in E. histolytica is limited. Lastly, we revised the gene models and annotated their 3′UTR in AmoebaDB, providing valuable resources to the community.