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

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.