title: Pre-spliceosomal binding of U1 small nuclear ribonucleoprotein (RNP) and heterogenous nuclear RNP E1 is associated with suppression of a growth hormone receptor pseudoexon.
abstract: Pseudoexons occur frequently in the human genome. This paper characterizes a pseudoexon in the GH receptor gene. Inappropriate activation of this pseudoexon causes Laron syndrome. Using in vitro splicing assays, pseudoexon silencing was shown to require a combination of a weak 5' pseudosplice-site and splicing silencing elements within the pseudoexon. Immunoprecipitation experiments showed that specific binding of heterogenous nuclear ribonucleoprotein E1 (hnRNP E1) and U1 small nuclear ribonucleoprotein (snRNP) in the pre-spliceosomal complex was associated with silencing of pseudoexon splicing. The possible role of hnRNP E1 was further supported by RNA interference experiments in cultured cells. Immunoprecipitation experiments with three other pseudoexons suggested that pre-spliceosomal binding of U1 snRNP is a potential general mechanism of suppression of pseudoexons.
authors.affiliation: Department of Endocrinology, 5th Floor, King George V Block, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, United Kingdom. s.a.akker@qmul.ac.uk
authors.forename: Scott A
authors.initials: SA
authors.lastname: Akker
authors.forename: Shivani
authors.initials: S
authors.lastname: Misra
authors.forename: Shazad
authors.initials: S
authors.lastname: Aslam
authors.forename: Emma L
authors.initials: EL
authors.lastname: Morgan
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Smith
authors.forename: Bernard
authors.initials: B
authors.lastname: Khoo
authors.forename: Shern L
authors.initials: SL
authors.lastname: Chew
mesh_terms: D004268:DNA-Binding Proteins; D005091:Exons; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D034622:RNA Interference; D022821:RNA Splice Sites; D012326:RNA Splicing; D012342:RNA, Small Nuclear / Q000378:metabolism; D016601:RNA-Binding Proteins; D011986:Receptors, Somatotropin / Q000235:genetics*; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism*; D017381:Spliceosomes / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C094604:PCBP1 protein, human; D022821:RNA Splice Sites; D012342:RNA, Small Nuclear; D016601:RNA-Binding Proteins; D011986:Receptors, Somatotropin; D017412:Ribonucleoprotein, U1 Small Nuclear