About: Retinitis Pigmentosa Mutations of SNRNP200 Enhance Cryptic Splice-Site Recognition

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	Mutations in SNRP200 gene cause autosomal-dominant retinal disorder retinitis pigmentosa (RP). The protein product of SNRNP200 is BRR2, a DExD/H box RNA helicase crucial for pre-mRNA splicing. In this study, we prepared p.S1087L and p.R1090L mutations of human BRR2 using bacterial artificial chromosome recombineering and stably expressed them in human cell culture. Mutations in BRR2 did not compromise snRNP assembly and both mutants were incorporated into the spliceosome just as the wild-type (wt) protein. Surprisingly, cells expressing RP mutants exhibited increased splicing efficiency of the LDHA gene. Next, we found that depletion of endogenous BRR2 enhanced usage of a β-globin cryptic splice site while splicing at the correct splice site was inhibited. Proper splicing of optimal and cryptic splice sites was restored in cells expressing BRR2-wt but not in cells expressing RP mutants. Taken together, our data suggest that BRR2 is an important factor in 5'-splice-site recognition and that the RP-linked mutations c.3260C>T (p.S1087L) and c.3269G>T (p.R1090L) affect this BRR2 function. Mutations in SNRP200 gene cause autosomal-dominant retinal disorder retinitis pigmentosa (RP). The protein product of SNRNP200 is BRR2, a DExD/H box RNA helicase crucial for pre-mRNA splicing. In this study, we prepared p.S1087L and p.R1090L mutations of human BRR2 using bacterial artificial chromosome recombineering and stably expressed them in human cell culture. Mutations in BRR2 did not compromise snRNP assembly and both mutants were incorporated into the spliceosome just as the wild-type (wt) protein. Surprisingly, cells expressing RP mutants exhibited increased splicing efficiency of the LDHA gene. Next, we found that depletion of endogenous BRR2 enhanced usage of a β-globin cryptic splice site while splicing at the correct splice site was inhibited. Proper splicing of optimal and cryptic splice sites was restored in cells expressing BRR2-wt but not in cells expressing RP mutants. Taken together, our data suggest that BRR2 is an important factor in 5'-splice-site recognition and that the RP-linked mutations c.3260C>T (p.S1087L) and c.3269G>T (p.R1090L) affect this BRR2 function. (en)
Title	Retinitis Pigmentosa Mutations of SNRNP200 Enhance Cryptic Splice-Site Recognition Retinitis Pigmentosa Mutations of SNRNP200 Enhance Cryptic Splice-Site Recognition (en)
skos:prefLabel	Retinitis Pigmentosa Mutations of SNRNP200 Enhance Cryptic Splice-Site Recognition Retinitis Pigmentosa Mutations of SNRNP200 Enhance Cryptic Splice-Site Recognition (en)
skos:notation	RIV/68378050:_____/14:00422663!RIV15-GA0-68378050
http://linked.open...avai/riv/aktivita	I P
http://linked.open...avai/riv/aktivity	I, P(GAP302/11/1910), P(GPP301/12/P425), P(KAN200520801)
http://linked.open...iv/cisloPeriodika	3
http://linked.open...vai/riv/dodaniDat	2015
http://linked.open...aciTvurceVysledku	Matějů, Daniel Cvačková, Zuzana Staněk, David
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Ústav molekulární genetiky AV ČR, v. v. i.
http://linked.open...dnocenehoVysledku	42557
http://linked.open...ai/riv/idVysledku	RIV/68378050:_____/14:00422663
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	Retinitis pigmentosa; pre-mRNA splicing; fidelity (en)
http://linked.open.../riv/klicoveSlovo	fidelity pre-mRNA splicing Retinitis pigmentosa
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[7C5F7647C169]
http://linked.open...i/riv/nazevZdroje	Human Mutation
http://linked.open...in/vavai/riv/obor	EB
http://linked.open...ichTvurcuVysledku	3 (xsd:int)
http://linked.open...cetTvurcuVysledku	3 (xsd:int)
http://linked.open...vavai/riv/projekt	Functional analysis of hBrr2 mutations linked to retinitis pigmentosa Targeted expression and transport of bioactive molecules Formation of splicing machinery in the context of the cell nucleus
http://linked.open...UplatneniVysledku	2014
http://linked.open...v/svazekPeriodika	35
http://linked.open...iv/tvurceVysledku	Staněk, David Cvačková, Zuzana Matějů, Daniel
http://linked.open...ain/vavai/riv/wos	000331909600008
issn	1059-7794
number of pages	10 (xsd:int)
http://bibframe.org/vocab/doi	10.1002/humu.22481

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