Pre-spliceosomal binding of U1 small nuclear ribonucleoprotein (RNP) and heterogenous nuclear RNP E1 is associated with suppression of a growth hormone receptor pseudoexon

被引：30

作者：

Akker, Scott A. ^{[1
]}

Misra, Shivani ^{[1
]}

Aslam, Shazad ^{[1
]}

Morgan, Emma L. ^{[1
]}

Smith, Philip J. ^{[1
]}

Khoo, Bernard ^{[1
]}

Chew, Shern L. ^{[1
]}

机构：

[1] St Bartholomews Hosp, Dept Endocrinol, London EC1A 7BE, England

来源：

MOLECULAR ENDOCRINOLOGY | 2007年 / 21卷 / 10期

基金：

英国惠康基金;

关键词：

D O I：

10.1210/me.2007-0038

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：2529 / 2540

页数：12

共 68 条

[1] Nuclear post-transcriptional control of gene expression [J].

Akker, SA ;

Smith, PJ ;

Chew, SL .

JOURNAL OF MOLECULAR ENDOCRINOLOGY, 2001, 27 (02) :123-131

[2] Bimolecular exon ligation by the human spliceosome [J].

Anderson, K ;

Moore, MJ .

SCIENCE, 1997, 276 (5319) :1712-1716

[3] Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1 [J].

Ars, E ;

Serra, E ;

García, J ;

Kruyer, H ;

Gaona, A ;

Lázaro, C ;

Estivill, X .

HUMAN MOLECULAR GENETICS, 2000, 9 (02) :237-247

[4] Creation of a novel donor splice site in intron 1 of the factor VIII gene leads to activation of a 191 bp cryptic exon in two haemophilia A patients [J].

Bagnall, RD ;

Waseem, NH ;

Green, PM ;

Colvin, B ;

Lee, C ;

Giannelli, F .

BRITISH JOURNAL OF HAEMATOLOGY, 1999, 107 (04) :766-771

[5] Analysis of BRCA1, TP53, and TSG101 germline mutations in German breast and/or ovarian cancer families [J].

Balz, V ;

Prisack, HB ;

Bier, H ;

Bojar, H .

CANCER GENETICS AND CYTOGENETICS, 2002, 138 (02) :120-127

[6]

BASERGASJ, 1993, RNA WORLD, P359

[7] SPLICING MUTANTS AND THEIR 2ND-SITE SUPPRESSORS AT THE DIHYDROFOLATE-REDUCTASE LOCUS IN CHINESE-HAMSTER OVARY CELLS [J].

CAROTHERS, AM ;

URLAUB, G ;

GRUNBERGER, D ;

CHASIN, LA .

MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (08) :5085-5098

[8] Listening to silence and understanding nonsense: Exonic mutations that affect splicing [J].

Cartegni, L ;

Chew, SL ;

Krainer, AR .

NATURE REVIEWS GENETICS, 2002, 3 (04) :285-298

[9] An intron element modulating 5' splice site selection in the hnRNP A1 pre-mRNA interacts with hnRNP A1 [J].

Chabot, B ;

Blanchette, M ;

Lapierre, I ;

LaBranche, H .

MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (04) :1776-1786

[10] An exonic splicing silencer in the testes-specific DNA ligase III β exon [J].

Chew, SL ;

Baginsky, L ;

Eperon, IC .

NUCLEIC ACIDS RESEARCH, 2000, 28 (02) :402-410

← 1 2 3 4 5 6 7 →