Nuclear cyclophilins affect spliceosome assembly and function in vitro.
Nuclear cyclophilins affect spliceosome assembly and function in vitro.
复制标题
DOI：
10.1042/bj20150396
复制
发表时间：
2015-07-15
期刊：
影响因子：
--
通讯作者：
Davis TL
中科院分区：
文献类型：
--
作者：
Adams BM;Coates MN;Jackson SR;Jurica MS;Davis TL
Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues. There are 17 annotated members of the cyclophilin family in humans, ubiquitously expressed and localized variously to the cytoplasm, nucleus or mitochondria. Surprisingly, all eight of the nuclear localized cyclophilins are found associated with spliceosomal complexes. However, their particular functions within this context are unknown. We have therefore adapted three established assays for in vitro pre-mRNA splicing to probe the functional roles of nuclear cyclophilins in the context of the human spliceosome. We find that four of the eight spliceosom-associated cyclophilins exert strong effects on splicing in vitro. These effects are dose-dependent and, remarkably, uniquely characteristic of each cyclophilin. Using both qualitative and quantitative means, we show that at least half of the nuclear cyclophilins can act as regulatory factors of spliceosome function in vitro. The present work provides the first quantifiable evidence that nuclear cyclophilins are splicing factors and provides a novel approach for future work into small molecule-based modulation of pre-mRNA splicing.
