Conservation and regulation of alternative splicing by dynamic inter- and intra-intron base pairings in Lepidoptera 14-3-3z pre-mRNAs

Conservation and regulation of alternative splicing by dynamic inter- and intra-intron base pairings in Lepidoptera 14-3-3z pre-mRNAs
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鳞翅目 14-3-3z 前体 mRNA 中动态内含子间和内含子碱基配对对选择性剪接的保护和调节

DOI:
10.4161/rna.20205
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发表时间:
2012-05
期刊:
影响因子:
4.1
通讯作者:
Shi F
Shi F
中科院分区:
生物学3区
文献类型:
--
作者:
Jin Y;Sun F;Wang X;Yue Y;Wang W;Zhang W;Zhan L;Tian N;Shi F

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前体mRNA的选择性剪接极大地促进了由单个基因产生的产物的多样性。然而,人们对潜在的调控机制知之甚少。在本研究中,我们描述了进化上保守的内含子内和内含子间RNA二级结构。突变实验表明,内含子内RNA二级结构导致空间位阻以执行相互剪接排他性,而内含子间RNA配对主要通过环出机制起作用。此外,相互排斥的剪接可以通过内含子内和内含子间的RNA配对竞争来调节。重要的是,产生的动态RNA结构在很大程度上控制互斥剪接,尽管顺式作用调控序列可以微调这一过程。我们的研究结果强调了动态RNA结构在选择性剪接中的重要性。
Alternative splicing of pre-mRNAs greatly contributes to diversity in products generated from a single gene. However, the underlying regulatory mechanisms are poorly understood. In the present study, we describe evolutionarily conserved intra-intronic and inter-intronic RNA secondary structures. Mutation experiments revealed that intra-intronic RNA secondary structure causes steric hindrance to enforce mutual splicing exclusivity, while inter-intronic RNA pairing largely functions through a looped-out mechanism. Moreover, mutually exclusive splicing may be regulated by RNA pairing competition between intra- and inter-introns. Importantly, the resulting dynamic RNA architecture largely controls mutually exclusive splicing, although cis-acting regulatory sequences may fine-tune this process. Our results emphasize the importance of dynamic RNA architecture in alternative splicing.
DOI: 10.1038/nature08909
发表时间: 2010-01-28
期刊: Nature
影响因子: 64.8
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DOI: 10.1261/rna.1812710
发表时间: 2010-01-01
期刊: RNA
影响因子: 4.5
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