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Published on: August 21, 2014
Multifunctional RNA processing protein SRm160 induces apoptosis and regulates eye and genital development in
Yu-Jie Fan1, Aryn H Gittis2, François Juge3
1Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 20032 Shanghai, China Université de Paris Sud 11, Unité Mixte de Recherche 8195, Université Paris XI, 91400 Orsay, France leonard.rabinow@u-psud.fr yjfan@sibs.ac.cn.
Abstract:
SRm160 is an SR-like protein implicated in multiple steps of RNA processing and nucleocytoplasmic export. Although its biochemical functions have been extensively described, its genetic interactions and potential participation in signaling pathways remain largely unknown, despite the fact that it is highly phosphorylated in both mammalian cells and Drosophila. To begin elucidating the functions of the protein in signaling and its potential role in developmental processes, we characterized mutant and overexpression SRm160 phenotypes in Drosophila and their interactions with the locus encoding the LAMMER protein kinase, Doa. SRm160 mutations are recessive lethal, while its overexpression generates phenotypes including roughened eyes and highly disorganized internal eye structure, which are due at least in part to aberrantly high levels of apoptosis. SRm160 is required for normal somatic sex determination, since its alleles strongly enhance a subtle sex transformation phenotype induced by Doa kinase alleles. Moreover, modification of SRm160 by DOA kinase appears to be necessary for its activity, since Doa alleles suppress phenotypes induced by SRm160 overexpression in the eye and enhance those in genital discs. Modification of SRm160 may occur through direct interaction because DOA kinase phosphorylates it in vitro. Remarkably, SRm160 protein was concentrated in the nuclei of precellular embryos but was very rapidly excluded from nuclei or degraded coincident with cellularization. Also of interest, transcripts are restricted almost exclusively to the developing nervous system in mature embryos.
Insights
SRm160, a protein involved in RNA processing, plays a crucial role in Drosophila development. Its interaction with the Doa kinase is vital for cell signaling, sex determination, and embryonic development.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- SRm160 is an SR-like protein involved in RNA processing and nucleocytoplasmic export.
- Its biochemical functions are known, but its role in signaling pathways and development is unclear, despite high phosphorylation in cells.
- Understanding SRm160's genetic interactions and signaling roles is crucial for developmental biology.
Purpose of the Study:
- To elucidate the signaling functions and developmental roles of SRm160 in Drosophila.
- To characterize phenotypes associated with SRm160 mutations and overexpression.
- To investigate the interaction between SRm160 and the LAMMER protein kinase, Doa.
Main Methods:
- Phenotypic characterization of SRm160 mutants and overexpression lines in Drosophila.
- Genetic interaction studies between SRm160 and Doa kinase.
- In vitro phosphorylation assays to determine DOA kinase activity on SRm160.
- Analysis of SRm160 protein localization during embryonic development.
Main Results:
- SRm160 mutations are recessive lethal; overexpression causes roughened eyes and increased apoptosis.
- SRm160 is essential for somatic sex determination, with alleles enhancing Doa kinase-induced sex transformation.
- DOA kinase modifies SRm160, impacting its activity in eye and genital disc development; direct phosphorylation was observed in vitro.
- SRm160 protein localizes to nuclei in early embryos but is excluded/degraded during cellularization; transcripts are found in the nervous system.
Conclusions:
- SRm160 is a key regulator in Drosophila development, influencing eye morphology, apoptosis, and sex determination.
- The interaction and phosphorylation of SRm160 by DOA kinase are critical for its function in various developmental processes.
- SRm160 exhibits dynamic subcellular localization during early embryogenesis, suggesting stage-specific roles.
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