Portal de Periódicos da CAPES

P68 RNA Helicase (DDX5) Alters Activity of Cis- and Trans-Acting Factors of the Alternative Splicing of H-Ras

2008; Public Library of Science; Volume: 3; Issue: 8 Linguagem: Inglês

10.1371/journal.pone.0002926

1932-6203

Maria Camats, Sònia Guil, Mariette Kokolo, Montse Bach‐Elias,

RNA modifications and cancer

H-Ras pre-mRNA undergoes an alternative splicing process to render two proteins, namely p21 H-Ras and p19 H-Ras, due to either the exclusion or inclusion of the alternative intron D exon (IDX), respectively. p68 RNA helicase (p68) is known to reduce IDX inclusion.Here we show that p68 unwinds the stem-loop IDX-rasISS1 structure and prevents binding of hnRNP H to IDX-rasISS1. We also found that p68 alters the dynamic localization of SC35, a splicing factor that promotes IDX inclusion. The knockdown of hnRNP A1, FUS/TLS and hnRNP H resulted in upregulation of the expression of the gene encoding the SC35-binding protein, SFRS2IP. Finally, FUS/TLS was observed to upregulate p19 expression and to stimulate IDX inclusion, and in vivo RNAi-mediated depletion of hnRNP H decreased p19 H-Ras abundance.Taken together, p68 is shown to be an essential player in the regulation of H-Ras expression as well as in a vital transduction signal pathway tied to cell proliferation and many cancer processes.