Minor class splicing shapes the zebrafish transcriptome during development

Markmiller, Sebastian, Cloonan, Nicole, Lardelli, Rea M., Doggett, Karen, Keightley, Maria-Cristina, Boglev, Yeliz, Trotter, Andrew J., Ng, Annie Y., Wilkins, Simon J., Verkade, Heather, Ober, Elke A., Field, Holly A., Grimmond, Sean M., Lieschke, Graham J., Stainier, Didier Y. R. and Heath, Joan K. (2014) Minor class splicing shapes the zebrafish transcriptome during development. Proceedings of the National Academy of Sciences of the United States of America, 111 8: 3062-3067. doi:10.1073/pnas.1305536111


Author Markmiller, Sebastian
Cloonan, Nicole
Lardelli, Rea M.
Doggett, Karen
Keightley, Maria-Cristina
Boglev, Yeliz
Trotter, Andrew J.
Ng, Annie Y.
Wilkins, Simon J.
Verkade, Heather
Ober, Elke A.
Field, Holly A.
Grimmond, Sean M.
Lieschke, Graham J.
Stainier, Didier Y. R.
Heath, Joan K.
Title Minor class splicing shapes the zebrafish transcriptome during development
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2014-02-25
Year available 2014
Sub-type Article (original research)
DOI 10.1073/pnas.1305536111
Volume 111
Issue 8
Start page 3062
End page 3067
Total pages 6
Publisher National Academy of Sciences
Collection year 2015
Language eng
Formatted abstract
Minor class or U12-type splicing is a highly conserved process required to remove a minute fraction of introns from human premRNAs. 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 05 Mar 2014, 10:29:08 EST by Susan Allen on behalf of Institute for Molecular Bioscience