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Functional characterization of ZNF183 on human spliceosome

Grant number: 11/20664-5
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): March 01, 2012
Effective date (End): June 30, 2012
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Carla Columbano de Oliveira
Grantee:Patricia Pereira Coltri
Supervisor: Melissa S. Jurica
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: University of California, Santa Cruz (UC Santa Cruz), United States  


Pre-RNA splicing is an essential step on gene regulation in eukaryotes. Splicing is the removal of introns and ligation of exons in mature RNA sequences and is performed by the spliceosome, a ~4 MDa macromolecular machinery composed of 5 snRNAs (small nuclear RNAs) and more than a hundred proteins, many of which are conserved from yeasts to mammals. Spliceosome assembly is a dynamic process, and formation of a catalytically competent complex is dependent on rearrangements of many RNA and proteins interactions. Understanding the role of these proteins and their association to the complex would greatly expand the current knowledge on splicing regulation. Among these proteins is ZNF183, orthologous to Saccharomyces cerevisiae Cwc24p. In vivo and in vitro analysis showed Cwc24p strongly affects pre-U3 snoRNA splicing in S. cerevisiae. Initial experiments with ZNF183 showed this protein is a component of human spliceosomes. However, the specific role of this protein as well as its association to this complex are currently unknown. To address these questions, the association of ZNF183 to human spliceosomes will be assessed. Assembly of the spliceosome and presence of the snRNAs on the complex will be tested under depletion of ZNF183. Additionally, full-lenght and truncated versions of ZNF183 will be used on in vitro reactions to analyze the contribution of the separate domains to the protein function. In a general context, these results will contribute to the understanding of ZNF183 role on assembly and activation of human spliceosomes. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GATTI DA SILVA, GUILHERME H.; JURICA, MELISSA S.; CHAGAS DA CUNHA, JULIA P.; OLIVEIRA, CARLA C.; COLTRI, PATRICIA P.. Human RNF113A participates of pre-mRNA splicing in vitro. Journal of Cellular Biochemistry, v. 120, n. 5, p. 8764-8774, . (10/51842-3, 13/02738-7, 11/20664-5, 17/06994-9)

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