P68 RNA Helicase DDX5 Alters Activity of Cis- and Trans-Acting Factors of the Alternative Splicing of H-RasReportar como inadecuado




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Background

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.

Principal Findings

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.

Significance

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.



Autor: Maria Camats , Sonia Guil , Mariette Kokolo, Montse Bach-Elias

Fuente: http://plos.srce.hr/



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