A novel mechanism of aberrant pre-mRNA splicing in humans

Human Molecular Genetics
J D CoganJ A Phillips

Abstract

Eukaryotic pre-mRNA splicing is regulated by consensus sequences at the intron boundaries and branch site. Recently, Sirand-Pugnet et al. reported the importance of an additional intronic sequence, an (A/U)GGG repeat in chicken beta-tropomyosin that is a binding site for a protein required for spliceosome assembly. Interestingly, we have detected mutations in IVS3 of the human growth hormone (GH) gene that affect a putative, homologous consensus sequence and which also perturb splicing. In a series of dominant-negative GH mutations that cause exon skipping, we found two mutations that do not occur within the 5' and 3' splice sites, or branch consensus sites. The first mutation is a G-->A transition of the 28th base (+28G-->A) of and the second deletes 18 bp (del+28-45) of IVS3 of the human GH gene. These mutations segregated with autosomal dominant GH deficiency in both kindreds and no other allelic GH gene changes were detected. RT-PCR amplification of transcripts from expression vectors containing the +28G-->A or del+28-45 alleles yielded products showing a >10-fold preferred use of alternative splicing, similar to findings previously reported for IVS3 donor site mutations. Both mutations are located 28 bp downstream from the...Continue Reading

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Sep 5, 1992·Journal of Molecular Biology·J EngelbrechtS Brunak
Feb 11, 1991·Nucleic Acids Research·M H PolymeropoulosC R Merril
Jan 1, 1989·Annual Review of Genetics·C W SmithB Nadal-Ginard
Jan 1, 1987·Methods in Enzymology·T A KunkelR A Zakour
Jan 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·T A Kunkel
Jan 1, 1974·Archives of Disease in Childhood·E M Poskitt, P H Rayner
Jan 22, 1982·Nucleic Acids Research·S M Mount

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Citations

Sep 27, 2002·Annals of Neurology·Grace M HobsonFranca Cambi
May 24, 2012·Genome Biology and Evolution·Rodger B VoelkerJ Andrew Berglund
Dec 13, 2006·Nucleic Acids Research·Roberto MarcucciMaurizio Romano
Oct 21, 2009·Current Opinion in Allergy and Clinical Immunology·Amy P HsuJulie E Niemela
Oct 18, 2007·Beilstein Journal of Organic Chemistry·Matthew J McGrath, Carsten Bolm
Feb 26, 2000·Journal of Pediatric Endocrinology & Metabolism : JPEM·H Abdul-LatifJ S Parks
Jan 29, 2011·Journal of Clinical Research in Pediatric Endocrinology·Primus E Mullis
Nov 30, 2006·European Journal of Endocrinology·James P G TurtonMehul T Dattani
Mar 15, 2005·European Journal of Endocrinology·Primus E Mullis
Dec 6, 2011·Indian Journal of Pediatrics·Kyriaki S Alatzoglou, Mehul T Dattani
Mar 15, 2011·Best Practice & Research. Clinical Endocrinology & Metabolism·Primus-E Mullis
Nov 4, 2010·European Journal of Medical Genetics·Mari Ann KulsethTrine Prescott
May 12, 2010·Molecular Genetics and Metabolism·Steven F DobrowolskiBrage S Andresen
Jan 17, 2009·Clinical Biochemistry·Aya MatsusueYoshihiro Miyake
Mar 6, 2007·Endocrinology and Metabolism Clinics of North America·Primus E Mullis
Apr 16, 1998·American Journal of Human Genetics·S HoffmeyerW Krone
Mar 27, 2002·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·N KatsumataT Tanaka
Sep 14, 2000·American Journal of Human Genetics·S M Mount
Jul 28, 2016·Biochemical Pharmacology·Maria Consolata MilettaPrimus-E Mullis
May 20, 2004·American Journal of Medical Genetics. Part a·Jocelyne M LewPaul D Sadowski
Nov 1, 2006·Bulletin of Experimental Biology and Medicine·O V FofanovaI I Dedov
Aug 31, 2002·Endocrine Journal·Yoshsitaka HayashiHisao Seo
Jun 8, 2010·Nature Structural & Molecular Biology·Cyril DominguezFrédéric H-T Allain
Sep 21, 2010·Nature Reviews. Endocrinology·Kyriaki S Alatzoglou, Mehul T Dattani
Oct 15, 1998·Nature Genetics·L Van LaerG Van Camp
Jan 24, 2014·Endocrine Reviews·Kyriaki S AlatzoglouMehul T Dattani
Jun 3, 2016·Endocrinology·Maria Consolata MilettaPrimus-E Mullis
Jul 3, 2002·Journal of Pediatric Endocrinology & Metabolism : JPEM·Michael P Wajnrajch
Feb 5, 2005·Médecine sciences : M/S·Claude Houdayer, Dominique Stoppa-Lyonnet
Aug 30, 2007·The Journal of Clinical Endocrinology and Metabolism·Vibor PetkovicPrimus E Mullis

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