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Minor class splicing shapes the zebrafish transcriptome during development

Citation

Markmiller, S and Cloonan, N and Lardelli, RM and Doggett, K and Keightley, M-C and Boglev, Y and Trotter, AJ and Ng, AY and Wilkins, SJ and Verkade, H and Ober, EA and Field, HA and Grimmond, SM and Lieschke, GJ and Stainiers, DYR and Heath, JK, Minor class splicing shapes the zebrafish transcriptome during development, National Academy of Sciences of The United States of America. Proceedings, 111, (8) pp. 3062-3067. ISSN 0027-8424 (2014) [Refereed Article]


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2014 The Authors

DOI: doi:10.1073/pnas.1305536111

Abstract

Minor class or U12-type splicing is a highly conserved process required to remove a minute fraction of introns from human pre-mRNAs. Defects in this splicing pathway have recently been linked to human disease, including a severe developmental disorder encompassing brain and skeletal abnormalities known as Taybi-Linder syndrome or microcephalic osteodysplastic primordial dwarfism 1, and a hereditary intestinal polyposis condition, Peutz-Jeghers syndrome. Although a key mechanism for regulating gene expression, the impact of impaired U12-type splicing on the transcriptome is unknown. Here, we describe a unique zebrafish mutant, caliban (clbn), with arrested development of the digestive organs caused by an ethylnitrosourea-induced recessive lethal point mutation in the rnpc3 [RNA-binding region (RNP1, RRM) containing 3] gene. rnpc3 encodes the zebrafish ortholog of human RNPC3, also known as the U11/U12 di-snRNP 65-kDa protein, a unique component of the U12-type spliceosome. The biochemical impact of the mutation in clbn is the formation of aberrant U11- and U12-containing small nuclear ribonucleoproteins that impair the efficiency of U12-type splicing. Using RNA sequencing and microarrays, we show that multiple genes involved in various steps of mRNA processing, including transcription, splicing, and nuclear export are disrupted in clbn, either through intron retention or differential gene expression. Thus, clbn provides a useful and specific model of aberrant U12-type splicing in vivo. Analysis of its transcriptome reveals efficient mRNA processing as a critical process for the growth and proliferation of cells during vertebrate development.

Item Details

Item Type:Refereed Article
Keywords:minor class splicing, zebrafish
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Biochemistry and Cell Biology not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Trotter, AJ (Dr Andrew Trotter)
ID Code:116386
Year Published:2014
Web of Science® Times Cited:14
Deposited By:IMAS - Directorate
Deposited On:2017-05-09
Last Modified:2017-07-31
Downloads:6 View Download Statistics

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