title: Multiple and specific mRNA processing targets for the major human hnRNP proteins.
abstract: Alternative splicing is a key mechanism regulating gene expression, and it is often used to produce antagonistic activities particularly in apoptotic genes. Heterogeneous nuclear ribonucleoparticle (hnRNP) proteins form a family of RNA-binding proteins that coat nascent pre-mRNAs. Many but not all major hnRNP proteins have been shown to participate in splicing control. The range and specificity of hnRNP protein action remain poorly documented, even for those affecting splice site selection. We used RNA interference and a reverse transcription-PCR screening platform to examine the implications of 14 of the major hnRNP proteins in the splicing of 56 alternative splicing events in apoptotic genes. Out of this total of 784 alternative splicing reactions tested in three human cell lines, 31 responded similarly to a knockdown in at least two different cell lines. On the other hand, the impact of other hnRNP knockdowns was cell line specific. The broadest effects were obtained with hnRNP K and C, two proteins whose role in alternative splicing had not previously been firmly established. Different hnRNP proteins affected distinct sets of targets with little overlap even between closely related hnRNP proteins. Overall, our study highlights the potential contribution of all of these major hnRNP proteins in alternative splicing control and shows that the targets for individual hnRNP proteins can vary in different cellular contexts.
authors.affiliation: Département de Microbiologie et d'Infectiologie, Faculté de Médecine et des Sciences de la Santé, 3001, 12th Avenue Nord, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada.
authors.forename: Julian P
authors.initials: JP
authors.lastname: Venables
authors.forename: Chu-Shin
authors.initials: CS
authors.lastname: Koh
authors.forename: Ulrike
authors.initials: U
authors.lastname: Froehlich
authors.forename: Elvy
authors.initials: E
authors.lastname: Lapointe
authors.forename: Sonia
authors.initials: S
authors.lastname: Couture
authors.forename: Lyna
authors.initials: L
authors.lastname: Inkel
authors.forename: Anne
authors.initials: A
authors.lastname: Bramard
authors.forename: Eric R
authors.initials: ER
authors.lastname: Paquet
authors.forename: Valérie
authors.initials: V
authors.lastname: Watier
authors.forename: Mathieu
authors.initials: M
authors.lastname: Durand
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Lucier
authors.forename: Julien
authors.initials: J
authors.lastname: Gervais-Bird
authors.forename: Karine
authors.initials: K
authors.lastname: Tremblay
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Prinos
authors.forename: Roscoe
authors.initials: R
authors.lastname: Klinck
authors.forename: Sherif Abou
authors.initials: SA
authors.lastname: Elela
authors.forename: Benoit
authors.initials: B
authors.lastname: Chabot
mesh_terms: D017398:Alternative Splicing; D020816:Amino Acid Motifs; D045744:Cell Line, Tumor; D015536:Down-Regulation; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016133:Polymerase Chain Reaction; D012322:RNA Precursors / Q000378:metabolism*
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012322:RNA Precursors