Universität zu Köln

Claudius, Ann-Katrin, Romani, Patrizia, Lamkemeyer, Tobias, Jindra, Marek ORCID: 0000-0002-2196-9924 and Uhlirova, Mirka ORCID: 0000-0002-5735-8287 (2014). Unexpected Role of the Steroid-Deficiency Protein Ecdysoneless in Pre-mRNA Splicing. PLoS Genet., 10 (4). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7404

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Abstract

The steroid hormone ecdysone coordinates insect growth and development, directing the major postembryonic transition of forms, metamorphosis. The steroid-deficient ecdysoneless 1 (ecd 1) strain of Drosophila melanogaster has long served to assess the impact of ecdysone on gene regulation, morphogenesis, or reproduction. However, ecd also exerts cell-autonomous effects independently of the hormone, and mammalian Ecd homologs have been implicated in cell cycle regulation and cancer. Why the Drosophila ecd 1 mutants lack ecdysone has not been resolved. Here, we show that in Drosophila cells, Ecd directly interacts with core components of the U5 snRNP spliceosomal complex, including the conserved Prp8 protein. In accord with a function in pre-mRNA splicing, Ecd and Prp8 are cell-autonomously required for survival of proliferating cells within the larval imaginal discs. In the steroidogenic prothoracic gland, loss of Ecd or Prp8 prevents splicing of a large intron from CYP307A2/spookier (spok) pre-mRNA, thus eliminating this essential ecdysone-biosynthetic enzyme and blocking the entry to metamorphosis. Human Ecd (hEcd) can substitute for its missing fly ortholog. When expressed in the Ecd-deficient prothoracic gland, hEcd re-establishes spok pre-mRNA splicing and protein expression, restoring ecdysone synthesis and normal development. Our work identifies Ecd as a novel pre-mRNA splicing factor whose function has been conserved in its human counterpart. Whether the role of mammalian Ecd in cancer involves pre-mRNA splicing remains to be discovered.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Claudius, Ann-Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Romani, Patrizia UNSPECIFIED UNSPECIFIED UNSPECIFIED Lamkemeyer, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Jindra, Marek UNSPECIFIED orcid.org/0000-0002-2196-9924 UNSPECIFIED Uhlirova, Mirka UNSPECIFIED orcid.org/0000-0002-5735-8287 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-442868
DOI:	10.1371/journal.pgen.1004287
Journal or Publication Title:	PLoS Genet.
Volume:	10
Number:	4
Date:	2014
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1553-7404
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DROSOPHILA-MELANOGASTER; SCHIZOSACCHAROMYCES-POMBE; RETINITIS-PIGMENTOSA; GENE; EXPRESSION; MUTATION; MATURATION; YEAST; IDENTIFICATION; TRANSCRIPTION Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/44286