Gutenberg Open Science: Pathogenic variants in USH1G/SANS alter protein interaction with pre-RNA processing factors PRPF6 and PRPF31 of the spliceosome

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-9925

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DC Field	Value	Language
dc.contributor.author	Fritze, Jacques S.	-
dc.contributor.author	Stiehler, Felizitas F.	-
dc.contributor.author	Wolfrum, Uwe	-
dc.date.accessioned	2024-01-12T10:17:04Z	-
dc.date.available	2024-01-12T10:17:04Z	-
dc.date.issued	2023	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/9943	-
dc.description.abstract	Pre-mRNA splicing is an essential process orchestrated by the spliceosome, a dynamic complex assembled stepwise on pre-mRNA. We have previously identified that USH1G protein SANS regulates pre-mRNA splicing by mediating the intranuclear transfer of the spliceosomal U4/U6.U5 tri-snRNP complex. During this process, SANS interacts with the U4/U6 and U5 snRNP-specific proteins PRPF31 and PRPF6 and regulates splicing, which is disturbed by variants of USH1G/SANS causative for human Usher syndrome (USH), the most common form of hereditary deaf–blindness. Here, we aim to gain further insights into the molecular interaction of the splicing molecules PRPF31 and PRPF6 to the CENTn domain of SANS using fluorescence resonance energy transfer assays in cells and in silico deep learning-based protein structure predictions. This demonstrates that SANS directly binds via two distinct conserved regions of its CENTn to the two PRPFs. In addition, we provide evidence that these interactions occur sequentially and a conformational change of an intrinsically disordered region to a short α-helix of SANS CENTn2 is triggered by the binding of PRPF6. Furthermore, we find that pathogenic variants of USH1G/SANS perturb the binding of SANS to both PRPFs, implying a significance for the USH1G pathophysiology.	en_GB
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	570 Biowissenschaften	de_DE
dc.subject.ddc	570 Life sciences	en_GB
dc.title	Pathogenic variants in USH1G/SANS alter protein interaction with pre-RNA processing factors PRPF6 and PRPF31 of the spliceosome	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-9925	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 10 Biologie	de
jgu.organisation.number	7970	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	International journal of molecular sciences	de
jgu.journal.volume	24	de
jgu.pages.alternative	17608	de
jgu.publisher.year	2023	-
jgu.publisher.name	MDPI	de
jgu.publisher.place	Basel	de
jgu.publisher.issn	1422-0067	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	570	de
jgu.publisher.doi	10.3390/ijms242417608	de
jgu.organisation.ror	https://ror.org/023b0x485	-
jgu.subject.dfg	Lebenswissenschaften	de
Appears in collections:	DFG-491381577-G

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