Pathogenic Variants in USH1G/SANS Alter Protein Interaction with Pre-RNA Processing Factors PRPF6 and PRPF31 of the Spliceosome

Publication type:
Journal article
Metadata:
Autoren
  • Jacques S Fritze
  • Felizitas F Stiehler
  • Uwe Wolfrum
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:001132163000001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.3390/ijms242417608
eISSN
1422-0067
Externe Identifier
  • Clarivate Analytics Document Solution ID: DL3Q3
  • PubMed Identifier: 38139438
ISSN
1661-6596
Ausgabe der Veröffentlichung
24
Zeitschrift
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Schlüsselwörter
  • splicing
  • U4/U6.U5 tri-snRNP
  • Usher syndrome
  • protein-protein interaction
  • FRET
  • AlphaFold2
  • in silico structure predictions
Artikelnummer
ARTN 17608
Datum der Veröffentlichung
2023
Status
Published
Titel
Pathogenic Variants in <i>USH1G</i>/SANS Alter Protein Interaction with Pre-RNA Processing Factors PRPF6 and PRPF31 of the Spliceosome
Sub types
  • Article
Ausgabe der Zeitschrift
24

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:p>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.</jats:p>
Autoren
  • Jacques S Fritze
  • Felizitas F Stiehler
  • Uwe Wolfrum
DOI
10.3390/ijms242417608
eISSN
1422-0067
Ausgabe der Veröffentlichung
24
Zeitschrift
International Journal of Molecular Sciences
Sprache
en
Online publication date
2023
Paginierung
17608 - 17608
Status
Published online
Herausgeber
MDPI AG
Herausgeber URL
http://dx.doi.org/10.3390/ijms242417608
Datum der Datenerfassung
2023
Titel
Pathogenic Variants in USH1G/SANS Alter Protein Interaction with Pre-RNA Processing Factors PRPF6 and PRPF31 of the Spliceosome
Ausgabe der Zeitschrift
24

Data source: Crossref

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 <i>USH1G</i> 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 <i>USH1G</i>/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 <i>USH1G</i>/SANS perturb the binding of SANS to both PRPFs, implying a significance for the <i>USH1G</i> pathophysiology.
Addresses
  • Institute of Molecular Physiology, Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
Autoren
  • Jacques S Fritze
  • Felizitas F Stiehler
  • Uwe Wolfrum
DOI
10.3390/ijms242417608
eISSN
1422-0067
Externe Identifier
  • PubMed Identifier: 38139438
  • PubMed Central ID: PMC10744108
Funding acknowledgements
  • Foundation Fighting Blindness: PPA-0717-0719-RAD
Open access
true
ISSN
1422-0067
Ausgabe der Veröffentlichung
24
Zeitschrift
International journal of molecular sciences
Schlüsselwörter
  • Spliceosomes
  • Humans
  • Ribonucleoprotein, U4-U6 Small Nuclear
  • Eye Proteins
  • Nerve Tissue Proteins
  • Transcription Factors
  • RNA Precursors
  • RNA Splicing
  • Usher Syndromes
  • HEK293 Cells
  • RNA Splicing Factors
Sprache
eng
Medium
Electronic
Online publication date
2023
Open access status
Open Access
Paginierung
17608
Datum der Veröffentlichung
2023
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2023
Titel
Pathogenic Variants in <i>USH1G</i>/SANS Alter Protein Interaction with Pre-RNA Processing Factors PRPF6 and PRPF31 of the Spliceosome.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
24

Files

https://www.mdpi.com/1422-0067/24/24/17608/pdf?version=1702969410 https://europepmc.org/articles/PMC10744108?pdf=render

Data source: Europe PubMed Central

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.
Date of acceptance
2023
Autoren
  • Jacques S Fritze
  • Felizitas F Stiehler
  • Uwe Wolfrum
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/38139438
DOI
10.3390/ijms242417608
eISSN
1422-0067
Externe Identifier
  • PubMed Central ID: PMC10744108
Funding acknowledgements
  • Foundation Fighting Blindness: PPA-0717-0719-RAD
Ausgabe der Veröffentlichung
24
Zeitschrift
Int J Mol Sci
Schlüsselwörter
  • AlphaFold2
  • FRET
  • U4/U6.U5 tri-snRNP
  • Usher syndrome
  • in silico structure predictions
  • protein–protein interaction
  • splicing
  • Humans
  • Eye Proteins
  • Nerve Tissue Proteins
  • Ribonucleoprotein, U4-U6 Small Nuclear
  • RNA Precursors
  • RNA Splicing
  • RNA Splicing Factors
  • Spliceosomes
  • Transcription Factors
  • Usher Syndromes
  • HEK293 Cells
Sprache
eng
Country
Switzerland
PII
ijms242417608
Datum der Veröffentlichung
2023
Status
Published online
Datum, an dem der Datensatz öffentlich gemacht wurde
2024
Titel
Pathogenic Variants in USH1G/SANS Alter Protein Interaction with Pre-RNA Processing Factors PRPF6 and PRPF31 of the Spliceosome.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
24

Data source: PubMed

Author's licence
CC-BY
Autoren
  • Jacques S Fritze
  • Felizitas F Stiehler
  • Uwe Wolfrum
Hosting institution
Universitätsbibliothek Mainz
Sammlungen
  • DFG-491381577-G
Resource version
Published version
DOI
10.3390/ijms242417608
File(s) embargoed
false
Open access
true
ISSN
1422-0067
Zeitschrift
International journal of molecular sciences
Schlüsselwörter
  • 570 Biowissenschaften
  • 570 Life sciences
Sprache
eng
Open access status
Open Access
Paginierung
17608
Datum der Veröffentlichung
2023
Public URL
https://openscience.ub.uni-mainz.de/handle/20.500.12030/9943
Herausgeber
MDPI
Datum der Datenerfassung
2024
Datum, an dem der Datensatz öffentlich gemacht wurde
2024
Zugang
Public
Titel
Pathogenic variants in USH1G/SANS alter protein interaction with pre-RNA processing factors PRPF6 and PRPF31 of the spliceosome
Ausgabe der Zeitschrift
24

Files

pathogenic_variants_in_ush1gs-20240112111445858.pdf

Data source: OPENSCIENCE.UB

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