RNA secondary structure in mutually exclusive splicing
RNA secondary structure in mutually exclusive splicing
复制标题
DOI：
10.1038/nsmb.1959
复制
发表时间：
2011-02-01
影响因子：
16.8
通讯作者：
Jin, Yongfeng
中科院分区：
文献类型：
--
作者：
Yang, Yun;Zhan, Leilei;Jin, Yongfeng
互斥剪接是产生蛋白质多样性的一种受调控的手段，但其潜在机制知之甚少。在此，比较基因组分析揭示了用于控制14-3-3 xi前mRNA的互斥剪接的内置内含子元件。这些元件是进化枝特异性的，但在二级结构水平上是进化保守的。综合证据显示，这些内含子间RNA配对的三重功能，协同确保多个外显子中的仅一个的选择，通过激活环外的近端可变外显子的近似顺式元件，并同时抑制环内的外显子，结合RNA配对的物理竞争。此外，在此模型下，我们还破译了Dscam（38，016种异构体）和Mhc（480种异构体）外显子簇4和9中的类似结构密码。我们的研究结果表明，一个广泛适用的机制，以确保互斥剪接。
Mutually exclusive splicing is a regulated means to generate protein diversity, but the underlying mechanisms are poorly understood. Here comparative genome analysis revealed the built-in intronic elements for controlling mutually exclusive splicing of the 14-3-3 xi pre-mRNA. These elements are clade specific but are evolutionarily conserved at the secondary structure level. Combined evidence revealed the triple functions of these inter-intronic RNA pairings in synergistically ensuring the selection of only one of multiple exons, through activation of the proximal variable exon outside the loop by the approximation of cis elements, and simultaneous repression of the exon within the loop, in combination with the physical competition of RNA pairing. Additionally, under this model, we also deciphered a similar structural code in exon clusters 4 and 9 of Dscam (38,016 isoforms) and Mhc (480 isoforms). Our findings suggest a broadly applicable mechanism to ensure mutually exclusive splicing.