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标题：Dramatically reduced spliceosome in Cyanidioschyzon merolae
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作者：Martha R. Stark ; Elizabeth A. Dunn ; William S. C. Dunn 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：11
页码：E1191-E1200
DOI：10.1073/pnas.1416879112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe spliceosome--the molecular particle responsible for removing interrupting sequences from eukaryotic messenger RNA--is one of the most complex cellular machines. Consisting of five snRNAs and over 200 proteins in humans, its numerous changes in composition and shape during splicing have made it difficult to study. We have characterized an algal spliceosome that is much smaller, with only 43 identifiable core proteins, the majority of which are essential for viability in other organisms. We propose that this highly reduced spliceosome has retained only the most critical splicing factors. Cyanidioschyzon merolae therefore provides a powerful system to examine the spliceosome's catalytic core, enabling future advances in understanding the splicing mechanism and spliceosomal organization that are challenging in more complex systems. The human spliceosome is a large ribonucleoprotein complex that catalyzes pre-mRNA splicing. It consists of five snRNAs and more than 200 proteins. Because of this complexity, much work has focused on the Saccharomyces cerevisiae spliceosome, viewed as a highly simplified system with fewer than half as many splicing factors as humans. Nevertheless, it has been difficult to ascribe a mechanistic function to individual splicing factors or even to discern which are critical for catalyzing the splicing reaction. We have identified and characterized the splicing machinery from the red alga Cyanidioschyzon merolae, which has been reported to harbor only 26 intron-containing genes. The U2, U4, U5, and U6 snRNAs contain expected conserved sequences and have the ability to adopt secondary structures and form intermolecular base-pairing interactions, as in other organisms. C. merolae has a highly reduced set of 43 identifiable core splicing proteins, compared with [~]90 in budding yeast and [~]140 in humans. Strikingly, we have been unable to find a U1 snRNA candidate or any predicted U1-associated proteins, suggesting that splicing in C. merolae may occur without the U1 small nuclear ribonucleoprotein particle. In addition, based on mapping the identified proteins onto the known splicing cycle, we propose that there is far less compositional variability during splicing in C. merolae than in other organisms. The observed reduction in splicing factors is consistent with the elimination of spliceosomal components that play a peripheral or modulatory role in splicing, presumably retaining those with a more central role in organization and catalysis.
关键词：pre-mRNA splicing ; spliceosome core ; U1 snRNP ; genome reduction ; splicing mechanism