Discovery of a pre-mRNA structural scaffold as a contributor to the mammalian splicing code.
Discovery of a pre-mRNA structural scaffold as a contributor to the mammalian splicing code.
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DOI：
10.1093/nar/gkab533
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发表时间：
2021-07-09
影响因子：
14.9
通讯作者：
Ghosh G
中科院分区：
文献类型：
--
作者：
Saha K;Fernandez MM;Biswas T;Joseph S;Ghosh G
剪接信号在外显子-内含子连接处或附近的特异性识别不能用它们的弱保守性来解释，而是假设需要大量嵌入前mRNA链中的特征。我们探讨了AdML的三维结构支架的可能性-一个模型前mRNA的底物指导早期剪接体成分的剪接信号序列。我们发现，在非同源剪接信号序列的突变阻碍招聘的早期spliceosomal组件由于破坏的全球结构的前mRNA。我们进一步发现，可能与早期剪接体组分U1 snRNP相互作用的pre-mRNA片段分布在整个内含子中，在pre-mRNA支架内存在5′和3′剪接位点的空间接近性，并且在募集早期剪接体组分时，结构支架和剪接调控元件之间存在相互作用。这些结果表明，早期的剪接体组件可以识别3D结构支架以外的短剪接信号序列，在我们的模型前mRNA，这种支架是跨内含子形成的主要剪接信号。这为分析可识别的3D结构支架对哺乳动物转录组中剪接密码的贡献提供了概念基础。
The specific recognition of splice signals at or near exon-intron junctions is not explained by their weak conservation and instead is postulated to require a multitude of features embedded in the pre-mRNA strand. We explored the possibility of 3D structural scaffold of AdML—a model pre-mRNA substrate—guiding early spliceosomal components to the splice signal sequences. We find that mutations in the non-cognate splice signal sequences impede recruitment of early spliceosomal components due to disruption of the global structure of the pre-mRNA. We further find that the pre-mRNA segments potentially interacting with the early spliceosomal component U1 snRNP are distributed across the intron, that there is a spatial proximity of 5′ and 3′ splice sites within the pre-mRNA scaffold, and that an interplay exists between the structural scaffold and splicing regulatory elements in recruiting early spliceosomal components. These results suggest that early spliceosomal components can recognize a 3D structural scaffold beyond the short splice signal sequences, and that in our model pre-mRNA, this scaffold is formed across the intron involving the major splice signals. This provides a conceptual basis to analyze the contribution of recognizable 3D structural scaffolds to the splicing code across the mammalian transcriptome.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
14.9
作者：
Cartegni, L;Wang, JH;Krainer, AR
通讯作者：
Krainer, AR
影响因子：
16.6
作者：
Cléry A;Krepl M;Nguyen CKX;Moursy A;Jorjani H;Katsantoni M;Okoniewski M;Mittal N;Zavolan M;Sponer J;Allain FH
通讯作者：
Allain FH
DOI：
10.1073/pnas.1017700108
发表时间：
2011-05-17
影响因子：
11.1
作者：
Cho, Suhyung;Hoang, Amy;Ghosh, Gourisankar
通讯作者：
Ghosh, Gourisankar
影响因子：
64.5
作者：
Baeza-Centurion, Pablo;Minana, Belen;Lehner, Ben
通讯作者：
Lehner, Ben