Remodeling of U2-U6 snRNA helix I during pre-mRNA splicing by Prp16 and the NineTeen Complex protein Cwc2.
Remodeling of U2-U6 snRNA helix I during pre-mRNA splicing by Prp16 and the NineTeen Complex protein Cwc2.
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DOI：
10.1093/nar/gku431
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发表时间：
2014-07
影响因子：
14.9
通讯作者：
O'Keefe RT
中科院分区：
文献类型：
--
作者：
Hogg R;de Almeida RA;Ruckshanthi JP;O'Keefe RT
从前信使RNA（pre-mRNA）去除内含子区域需要剪接体与前mRNA组装，然后随后剪接体重塑以允许激活内含子去除的两个步骤。剪接体重塑通过调节RNA-RNA和蛋白质-RNA相互作用的DExD/H-box ATP酶的作用进行。ATP酶Prp 16通过催化第一步因子Yju 2和Cwc 25的释放以及使U2-U6 snRNA螺旋I不稳定来重塑剪接的第一和第二步骤之间的剪接体。Prp 16如何使U2-U6螺旋I不稳定尚不清楚。我们发现，NineTeen复合物（NTC）蛋白Cwc 2显示与U6 ACAGAGA，U6内部茎环（ISL）和U2-U6螺旋I，所有形成剪接体活性位点的RNA元件的遗传相互作用。我们发现Cwc 2的一个功能是在剪接过程中稳定U2-U6 snRNA螺旋I。Cwc 2还与NTC蛋白Isy 1/NTC 30功能性地合作。Cwc 2突变可以抑制prp 16 -302突变的冷敏感表型，表明Cwc 2和Prp 16之间的功能联系。具体地说，Prp 16中的prp 16 -302突变稳定了Cwc 2与U6 snRNA的相互作用，并使Cwc 2与前mRNA的相互作用不稳定，表明Cwc 2和Prp 16的拮抗功能。我们建议，Cwc 2是一个目标Prp 16介导的剪接体重塑在前mRNA剪接。
Removal of intron regions from pre-messenger RNA (pre-mRNA) requires spliceosome assembly with pre-mRNA, then subsequent spliceosome remodeling to allow activation for the two steps of intron removal. Spliceosome remodeling is carried out through the action of DExD/H-box ATPases that modulate RNA–RNA and protein–RNA interactions. The ATPase Prp16 remodels the spliceosome between the first and second steps of splicing by catalyzing release of first step factors Yju2 and Cwc25 as well as destabilizing U2-U6 snRNA helix I. How Prp16 destabilizes U2-U6 helix I is not clear. We show that the NineTeen Complex (NTC) protein Cwc2 displays genetic interactions with the U6 ACAGAGA, the U6 internal stem loop (ISL) and the U2-U6 helix I, all RNA elements that form the spliceosome active site. We find that one function of Cwc2 is to stabilize U2-U6 snRNA helix I during splicing. Cwc2 also functionally cooperates with the NTC protein Isy1/NTC30. Mutation in Cwc2 can suppress the cold sensitive phenotype of the prp16-302 mutation indicating a functional link between Cwc2 and Prp16. Specifically the prp16-302 mutation in Prp16 stabilizes Cwc2 interactions with U6 snRNA and destabilizes Cwc2 interactions with pre-mRNA, indicating antagonistic functions of Cwc2 and Prp16. We propose that Cwc2 is a target for Prp16-mediated spliceosome remodeling during pre-mRNA splicing.
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