Characterization of the role of proteins involved in splicing regulation in eukaryotes

• Grant number: 13/02738-7
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2013
• End date: May 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Patricia Pereira Coltri
• Grantee: Patricia Pereira Coltri
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Carla Columbano de Oliveira ; Edna Teruko Kimura

Abstract

Pre-RNA splicing is an essential step on gene regulation in eukaryotes. The removal of introns and ligation of exons in mature RNA sequences is performed by the spliceosome, a ~4 MDa macromolecular machinery composed of 5 snRNAs (small nuclear RNAs) and more than a hundred proteins. The spliceosome must assemble on every intron that will be removed from the precursor transcript. Spliceosome assembly is a dynamic process, and formation of a catalytically competent complex is dependent on rearrangements of many RNA and proteins interactions. Until now core proteins found on spliceosomes assembled on introns of different transcripts have been considered identical. However, recent data suggests spliceosome composition may vary according to the transcript. Our hypothesis is that different transcripts recruit specific proteins that could regulate spliceosome activity and splicing. Understanding the role of these proteins and their association with specific transcripts would greatly expand the current knowledge on splicing regulation. Most of the eukaryotic transcripts contain non coding sequences inside the introns, important for control and regulation of genetic expression and cellular maintenance. Changes on the transcription profile or processing of these transcripts might cause several different diseases. In this proposal, regulation of splicing of introns containing small nucleolar RNAs and non-coding RNAs will be addressed. The role of proteins specifically recruited on such transcripts during splicing will be characterized. This proposal will investigate the association of these proteins in the complex as well as their activity on splicing. In a broader context, these results will contribute to the understanding of the mechanisms governing spliceosome regulation and activation, developing a new research program. (AU)

Scientific publications

(4)

(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)

PIRES, MATHIAS M.; CANTOR, MAURICIO; GUIMARAES, PAULO R.; DE AGUIAR, MARCUS A. M.; DOS REIS, SERGIO F.; COLTRI, PATRICIA P.. The network organization of protein interactions in the spliceosome is reproduced by the simple rules of food-web models. SCIENTIFIC REPORTS, v. 5, OCT 7 2015. (09/54422-8, 13/02738-7)

CANTOR, MAURICIO; PIRES, MATHIAS M.; MARQUITTI, FLAVIA M. D.; RAIMUNDO, RAFAEL L. G.; SEBASTIAN-GONZALEZ, ESTHER; COLTRI, PATRICIA P.; PEREZ, S. IVAN; BARNECHE, DIEGO R.; BRANDT, DEBORA Y. C.; NUNES, KELLY; et al. Nestedness across biological scales. PLoS One, v. 12, n. 2, FEB 6 2017. (15/11985-3, 14/21106-4, 11/11346-0, 11/13054-6, 13/02738-7, 13/22016-6, 09/54422-8, 12/09950-9)

PAIVA, MARCELO M.; KIMURA, EDNA T.; COLTRI, PATRICIA P.. miR18a and miR19a Recruit Specific Proteins for Splicing in Thyroid Cancer Cells. CANCER GENOMICS & PROTEOMICS, v. 14, n. 5, p. 373-381, SEP-OCT 2017. (17/06994-9, 13/02738-7)

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, MAY 2019. (10/51842-3, 13/02738-7, 11/20664-5, 17/06994-9)