Journal article
Early developmental arrest and impaired gastrointestinal homeostasis in U12-dependent splicing-defective Rnpc3-deficient mice
K Doggett, BB Williams, S Markmiller, FS Geng, J Coates, S Mieruszynski, M Ernst, T Thomas, JK Heath
RNA | COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT | Published : 2018
Abstract
Splicing is an essential step in eukaryotic gene expression. While the majority of introns is excised by the U2-dependent, or major class, spliceosome, the appropriate expression of a very small subset of genes depends on U12-dependent, or minor class, splicing. The U11/U12 65K protein (hereafter 65K), encoded by RNPC3, is one of seven proteins that are unique to the U12-dependent spliceosome, and previous studies including our own have established that it plays a role in plant and vertebrate development. To pinpoint the impact of 65K loss during mammalian development and in adulthood, we generated germline and conditional Rnpc3-deficient mice. Homozygous Rnpc3−/− embryos died prior to blast..
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Awarded by Ludwig Institute for Cancer Research
Funding Acknowledgements
The authors thank Andrew Naughton, Melanie Asquith, Mel Pritchard, Emily Sutherland, and Faye Dobrowski (mouse husbandry), Cary Tsui (histology), Qian Du, Lotta Burstroem, Julia Griesbach, and Samantha Eccles (technical assistance), and Anne Voss and Michael Buchert (helpful discussions). We also thank Drs. Stephen Scherer and Daniele Merico for providing us with their list of 822 human U12-type introns distributed across 744 genes. Rnpc3-targeted mice were generated and analyzed in collaboration with the European Conditional Mouse Mutagenesis Consortium (EUCOMM) and the Monash and Melbourne University nodes of the Australian Phenomics Network (APN). This work was supported by the National Health and Medical Research Council of Australia (grant 1024878 and Senior Research Fellowship 1022870 to J.K.H.), Ludwig Cancer Research and a Victorian State Government Operational Infrastructure Support grant.