P68 RNA helicase (DDX5) alters activity of cis- and trans-acting factors of the alternative splicing of H-Ras

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 s...

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Bibliographic Details
Published in:PloS one 2008-08, Vol.3 (8), p.e2926-e2926
Main Authors: Camats, Maria, Guil, Sonia, Kokolo, Mariette, Bach-Elias, Montse
Format: Article
Language:English
Subjects:
Abundance
Alternative Splicing
Base Sequence
Binding
Biochemistry/RNA Structure
Bioinformatics
Cancer
Cell cycle
Cell Division - genetics
Cell growth
Cell proliferation
DEAD-box RNA Helicases - metabolism
Deoxyribonucleic acid
DNA
DNA helicase
Experiments
FUS protein
Gene expression
Genes
Genes, ras
Genetic aspects
Genomes
H(+)-K(+)-Exchanging ATPase - metabolism
H-Ras protein
Heterogeneous-Nuclear Ribonucleoproteins - genetics
Heterogeneous-Nuclear Ribonucleoproteins - metabolism
Kinases
Kinetics
Localization
Messenger RNA
Molecular Biology/RNA Splicing
Molecular Biology/RNA-Protein Interactions
Molecular Sequence Data
mRNA
Mutation
Protein binding
Proteins
Ribonucleic acid
RNA
RNA helicase
RNA Precursors - genetics
RNA-mediated interference
Signal processing
Signal transduction
Splicing factors
Studies
Transduction
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0002926