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Nuclear Cyclophilins Impact Spliceosome Assembly and Function {Less than}i{Greater than}In Vitro{Less than}/i{Greater than}

Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyze cis/trans isomerization of proline residues. There are seventeen 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 spliceosomal-associated cyclophilins exert strong effects on splicing in vitro. These effects are dose-dependent and, remarkably, uniquely characteristic to 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. This 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.

Authors:   Adams B; Coates M; Jackson S; Jurica M; Davis T
Journal:   Biochemical Journal
Year:   2015
DOI:   10.1042/BJ20150396
Publication date:   13-May-2015
Facts, background information, dossiers
  • spliceosome
  • proteins
  • mitochondria
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