Spliceosome assembly and regulation: insights from analysis of highly reduced spliceosomes
- Corbin S. Black1,2,
- Thomas A. Whelan3,
- Erin L. Garside4,
- Andrew M. MacMillan4,
- Naomi M. Fast3 and
- Stephen D. Rader1
- 1Department of Chemistry and Biochemistry, University of Northern British Columbia, Prince George, British Columbia, Canada V2N 4Z9
- 2Department of Anatomy and Cell Biology, McGill University, Montréal, Quebec, Canada H3A 0C7
- 3Biodiversity Research Center and Department of Botany, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4
- 4Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
- Corresponding authors: rader{at}unbc.ca, amacmill{at}ualberta.ca, nfast{at}mail.ubc.ca
Abstract
Premessenger RNA splicing is catalyzed by the spliceosome, a multimegadalton RNA–protein complex that assembles in a highly regulated process on each intronic substrate. Most studies of splicing and spliceosomes have been carried out in human or S. cerevisiae model systems. There exists, however, a large diversity of spliceosomes, particularly in organisms with reduced genomes, that suggests a means of analyzing the essential elements of spliceosome assembly and regulation. In this review, we characterize changes in spliceosome composition across phyla, describing those that are most frequently observed and highlighting an analysis of the reduced spliceosome of the red alga Cyanidioschyzon merolae. We used homology modeling to predict what effect splicing protein loss would have on the spliceosome, based on currently available cryo-EM structures. We observe strongly correlated loss of proteins that function in the same process, for example, in interacting with the U1 snRNP (which is absent in C. merolae), regulation of Brr2, or coupling transcription and splicing. Based on our observations, we predict splicing in C. merolae to be inefficient, inaccurate, and post-transcriptional, consistent with the apparent trend toward its elimination in this lineage. This work highlights the striking flexibility of the splicing pathway and the spliceosome when viewed in the context of eukaryotic diversity.
Keywords
- Cyanidioschyzon merolae
- homology modeling
- reduced spliceosomes
- spliceosome diversity
- spliceosome structure
This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
