Drosophila splicing factor SF2 knock‐down mutant shows altered cell‐cycle in vivo

Abstract

Pioneering single gene study documents pre-mRNA processing proteins participation in the cell-cycle regulation of multi-cellular animals (Andersen and Tapon, 2008, J Biol Chem 283: 31256-67). Whole-genome RNAi screen in Drosophila tissue-culture cell lines demonstrates that 17 genes involved in RNA-processing are required for G2/M check-point function (Kondo and Perrimon, 2011, Sci Signal 4: rs1). In particular, the silencing of Splicing Factor 2 (SF2) increases the number of G2(M) cells. We have measured the absolute duration of cell-cycle phases in SF2 depleted flies with the use of flow cytometry and growth parameters of GFP marked mosaic clones. For SF2 mutant cells, G1 = 1.89 h, G2(M) = 7.22 h and S = 1.30 h compared with G1 = 2.25 h, G2(M) = 4.86 h and S = 1.28 h for control normal cells. Thus, G2(M) phase appears to be longer in SF2 silenced cells, supporting the evidence that this splicing protein participates in G2-M check-point function.

The Splicing Factor SF2 Is Critical for Hyperproliferation and Survival in a TORC1-Dependent Model of Early Tumorigenesis in Drosophila

“…SF2 is the Drosophila homolog of the proto-oncogene SRSF1. Silencing of SF2 has been shown to increase the number of G2/M cells and the length of G2/M phase in cultured Drosophila cell lines [ 26 ] and in eye and wing imaginal discs [ 27 ]. It is therefore likely that the apoptosis of Pten mutant cells with an SF2 knockdown is linked to a cell-cycle arrest at G2/M.…”

Alternative Splicing Regulation of Cancer-Related Pathways inCaenorhabditis elegans: An In Vivo Model System with a Powerful Reverse Genetics Toolbox

“…DNA topoisomerase I was identified as an SR protein kinase in HeLa cell extracts [66]. It was found to phosphorylate splicing factors involved in cell cycle regulation, such as SF2/ASF [67, 68]. It may be possible that these isoforms are working more closely than originally thought if one or both of the top-1 isoforms affect the cell cycle and carry the same SR kinase activity as shown in HeLa cells.…”