An Ancient Mechanism for Splicing Control: U11 snRNP as an Activator of Alternative Splicing
An Ancient Mechanism for Splicing Control: U11 snRNP as an Activator of Alternative Splicing
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DOI：
10.1016/j.molcel.2010.02.014
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发表时间：
2010-03-26
期刊：
影响因子：
16
通讯作者：
Frilander, Mikko J.
中科院分区：
文献类型：
--
作者：
Verbeeren, Jens;Niemela, Elina H.;Frilander, Mikko J.
选择性前mrna剪接通常由特定的蛋白质因子调控，这些蛋白因子识别前mrna中独特的序列元件，并直接或间接地影响附近剪接位点的使用。我们发现，u12型内含子的5‘剪接位点序列（5’ss）串联重复时，形成U11 snrnp结合剪接增强子USSE。U11与USSE的结合通过激活上游3's来调节u2型内含子的选择性剪接。USSE中的U12-type 5 s-like序列具有调节作用，不具有剪接供体的功能。USSEs存在于编码U11/U12非snRNP特异性48K和65K蛋白的动物和植物基因中，产生敏感开关，响应细胞内功能1111 snRNP水平，并改变48K和65K mrna的稳定性。我们得出结论，U11不仅在组成剪接中起5's识别的作用，而且还作为u12依赖性剪接体的激活剂和u12依赖性剪接体的调节剂。
Alternative pre-mRNA splicing is typically regulated by specific protein factors that recognize unique sequence elements in pre-mRNA and affect, directly or indirectly, nearby splice site usage. We show that 5' splice site sequences (5'ss) of U12-type introns, when repeated in tandem, form a U11 snRNP-binding splicing enhancer, USSE. Binding of U11 to the USSE regulates alternative splicing of U2-type introns by activating an upstream 3'ss. The U12-type 5'ss-like sequences within the USSE have a regulatory role and do not function as splicing donors. USSEs, present both in animal and plant genes encoding the U11/U12 di-snRNP-specific 48K and 65K proteins, create sensitive switches that respond to intracellular levels of functional 1111 snRNP and alter the stability of 48K and 65K mRNAs. We conclude that U11 functions not only in 5'ss recognition in constitutive splicing, but also as an activator of U2-dependent alternative splicing and as a regulator of the U12-dependent spliceosome.