SF1 mutations spectrum in cancer and implications on its subcellular localization and splicing function

• Grant number: 18/07525-5
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2018
• Effective date (End): January 31, 2020
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Leticia Fröhlich Archangelo
• Grantee: Lucca Zaghi de Oliveira
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/01458-3 - Defining the functional role of the splicing factor regulator (KIS) during leukemogenesis using a murine bone marrow transplantion model, AP.JP

Abstract

The SF1 protein recognizes the introns 3' regions during early stages of the spliceosome formation, but it is not required to constitutive splicing of all pre-mRNA in cells. Thus, SF1 acts as an alternative splicing factor on a cellular subset of pre-mRNAs. Besides acting on splicing, other functions have been described for SF1 in RNA nuclear retention and transcriptional repression. In addition, SF1 involvement in tumorigenesis was also evidenced. Somatic mutations in several genes related to splicing process, including SF1 and SF3b, were recently described in hematological diseases, consolidating splicing machinery defects as a new leukaemogenesis mechanism.Only for SF1 gene, 5 distinct mutations were identified in paciente samples with myelodysplasias (MDS), acute myeloid leukaemia (AML) e myeloproliferative disease (MPD) (Yoshida et al. 2011). The functional consequence of these mutations, that is, wether they cause gain or loss of function, as well as if they impact the various functions described to SF1, is still unknown.