Determination of global RNA splicing in SF1 overexpressed cells by RNA-seq

• Grant number: 17/23589-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Effective date (Start): February 01, 2018
• Effective date (End): May 31, 2018
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Leticia Fröhlich Archangelo
• Grantee: Guilherme Brussolo Bidoia
• Supervisor: Philipp Greif
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Ludwig Maximilian University of Munich (LMU Munich), Germany
• Associated to the scholarship: 16/03982-7 - Cloning SF1 wild type and mutated G372v and T454M in bicistronic retroviral vector for retrovirus production, BP.IC

Abstract

Splicing Factor 1 is located on chromosome 11q13. The protein contains an ULM motif, a coiled-coil and KH-QUA2 domains, followed by a zinc knuckle and a proline rich region. SF1 recognizes the branch point sequence within the intron, interacts with the U2AF subunits and signals the first steps of spliceosome assembly. In the alternative splicing, SF1 selectively regulates a subset of introns. Besides, SF1 plays a role in pre-mRNA retention and transcriptional repression. Recently, somatic mutations within SF1 were reported in patients with myelodysplastic syndromes, de novo acute myeloid leukemia and myeloproliferative neoplasms. Also, preliminary data from our group shows an increased SF1 expression in patients with acute lymphoid leukemia. In order to get further insights into SF1 function and possible role in leukemogenesis, the aim of this project is to identify the splicing and transcriptional targets of SF1 in lymphoid cell line overexpressing this protein. (AU)