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SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation

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SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation. / Nashabat, Marwan; Nabavizadeh, Nasrinsadat; Saraçoğlu, Hilal Pırıl; Sarıbaş, Burak; Avcı, Şahin; Börklü, Esra; Beillard, Emmanuel; Yılmaz, Elanur; Uygur, Seyide Ecesu; Kayhan, Cavit Kerem; Bosco, Luca; Eren, Zeynep Bengi; Steindl, Katharina; Richter, Manuela Friederike; Bademci, Guney; Rauch, Anita; Fattahi, Zohreh; Valentino, Maria Lucia; Connolly, Anne M; Bahr, Angela; Viola, Laura; Bergmann, Anke Katharina; Rocha, Maria Eugenia; Peart, LeShon; Castro-Rojas, Derly Liseth; Bültmann, Eva; Khan, Suliman; Giarrana, Miriam Liliana; Teleanu, Raluca Ioana; Gonzalez, Joanna Michelle; Pini, Antonella; Schädlich, Ines Sophie; Vill, Katharina; Brugger, Melanie; Zuchner, Stephan; Pinto, Andreia; Donkervoort, Sandra; Bivona, Stephanie Ann; Riza, Anca; Streata, Ioana; Gläser, Dieter; Baquero-Montoya, Carolina; Garcia-Restrepo, Natalia; Kotzaeridou, Urania; Brunet, Theresa; Epure, Diana Anamaria; Bertoli-Avella, Aida; Kariminejad, Ariana; Tekin, Mustafa; von Hardenberg, Sandra; Bönnemann, Carsten G; Stettner, Georg M; Zanni, Ginevra; Kayserili, Hülya; Oflazer, Zehra Piraye; Escande-Beillard, Nathalie; Undiagnosed Diseases Network.

in: NAT COMMUN, Jahrgang 15, Nr. 1, 27.02.2024, S. 1758.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Nashabat, M, Nabavizadeh, N, Saraçoğlu, HP, Sarıbaş, B, Avcı, Ş, Börklü, E, Beillard, E, Yılmaz, E, Uygur, SE, Kayhan, CK, Bosco, L, Eren, ZB, Steindl, K, Richter, MF, Bademci, G, Rauch, A, Fattahi, Z, Valentino, ML, Connolly, AM, Bahr, A, Viola, L, Bergmann, AK, Rocha, ME, Peart, L, Castro-Rojas, DL, Bültmann, E, Khan, S, Giarrana, ML, Teleanu, RI, Gonzalez, JM, Pini, A, Schädlich, IS, Vill, K, Brugger, M, Zuchner, S, Pinto, A, Donkervoort, S, Bivona, SA, Riza, A, Streata, I, Gläser, D, Baquero-Montoya, C, Garcia-Restrepo, N, Kotzaeridou, U, Brunet, T, Epure, DA, Bertoli-Avella, A, Kariminejad, A, Tekin, M, von Hardenberg, S, Bönnemann, CG, Stettner, GM, Zanni, G, Kayserili, H, Oflazer, ZP, Escande-Beillard, N & Undiagnosed Diseases Network 2024, 'SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation', NAT COMMUN, Jg. 15, Nr. 1, S. 1758. https://doi.org/10.1038/s41467-024-45933-5

APA

Nashabat, M., Nabavizadeh, N., Saraçoğlu, H. P., Sarıbaş, B., Avcı, Ş., Börklü, E., Beillard, E., Yılmaz, E., Uygur, S. E., Kayhan, C. K., Bosco, L., Eren, Z. B., Steindl, K., Richter, M. F., Bademci, G., Rauch, A., Fattahi, Z., Valentino, M. L., Connolly, A. M., ... Undiagnosed Diseases Network (2024). SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation. NAT COMMUN, 15(1), 1758. https://doi.org/10.1038/s41467-024-45933-5

Vancouver

Nashabat M, Nabavizadeh N, Saraçoğlu HP, Sarıbaş B, Avcı Ş, Börklü E et al. SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation. NAT COMMUN. 2024 Feb 27;15(1):1758. https://doi.org/10.1038/s41467-024-45933-5

Bibtex

@article{f6bd8bfbb8844c12b27eb12697c85337,
title = "SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation",
abstract = "SNURPORTIN-1, encoded by SNUPN, plays a central role in the nuclear import of spliceosomal small nuclear ribonucleoproteins. However, its physiological function remains unexplored. In this study, we investigate 18 children from 15 unrelated families who present with atypical muscular dystrophy and neurological defects. Nine hypomorphic SNUPN biallelic variants, predominantly clustered in the last coding exon, are ascertained to segregate with the disease. We demonstrate that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients' primary fibroblasts and CRISPR/Cas9-mediated mutant cell lines. Additionally, mutant nuclei exhibit defective spliceosomal maturation and breakdown of Cajal bodies. Transcriptome analyses reveal splicing and mRNA expression dysregulation, particularly in sarcolemmal components, causing disruption of cytoskeletal organization in mutant cells and patient muscle tissues. Our findings establish SNUPN deficiency as the genetic etiology of a previously unrecognized subtype of muscular dystrophy and provide robust evidence of the role of SPN1 for muscle homeostasis.",
keywords = "Child, Humans, Muscular Dystrophies/genetics, Ribonucleoproteins, Small Nuclear/metabolism, RNA/metabolism, RNA Splicing/genetics, Spliceosomes/genetics",
author = "Marwan Nashabat and Nasrinsadat Nabavizadeh and Sara{\c c}oğlu, {Hilal Pırıl} and Burak Sarıba{\c s} and {\c S}ahin Avcı and Esra B{\"o}rkl{\"u} and Emmanuel Beillard and Elanur Yılmaz and Uygur, {Seyide Ecesu} and Kayhan, {Cavit Kerem} and Luca Bosco and Eren, {Zeynep Bengi} and Katharina Steindl and Richter, {Manuela Friederike} and Guney Bademci and Anita Rauch and Zohreh Fattahi and Valentino, {Maria Lucia} and Connolly, {Anne M} and Angela Bahr and Laura Viola and Bergmann, {Anke Katharina} and Rocha, {Maria Eugenia} and LeShon Peart and Castro-Rojas, {Derly Liseth} and Eva B{\"u}ltmann and Suliman Khan and Giarrana, {Miriam Liliana} and Teleanu, {Raluca Ioana} and Gonzalez, {Joanna Michelle} and Antonella Pini and Sch{\"a}dlich, {Ines Sophie} and Katharina Vill and Melanie Brugger and Stephan Zuchner and Andreia Pinto and Sandra Donkervoort and Bivona, {Stephanie Ann} and Anca Riza and Ioana Streata and Dieter Gl{\"a}ser and Carolina Baquero-Montoya and Natalia Garcia-Restrepo and Urania Kotzaeridou and Theresa Brunet and Epure, {Diana Anamaria} and Aida Bertoli-Avella and Ariana Kariminejad and Mustafa Tekin and {von Hardenberg}, Sandra and B{\"o}nnemann, {Carsten G} and Stettner, {Georg M} and Ginevra Zanni and H{\"u}lya Kayserili and Oflazer, {Zehra Piraye} and Nathalie Escande-Beillard and {Undiagnosed Diseases Network}",
note = "{\textcopyright} 2024. The Author(s).",
year = "2024",
month = feb,
day = "27",
doi = "10.1038/s41467-024-45933-5",
language = "English",
volume = "15",
pages = "1758",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation

AU - Nashabat, Marwan

AU - Nabavizadeh, Nasrinsadat

AU - Saraçoğlu, Hilal Pırıl

AU - Sarıbaş, Burak

AU - Avcı, Şahin

AU - Börklü, Esra

AU - Beillard, Emmanuel

AU - Yılmaz, Elanur

AU - Uygur, Seyide Ecesu

AU - Kayhan, Cavit Kerem

AU - Bosco, Luca

AU - Eren, Zeynep Bengi

AU - Steindl, Katharina

AU - Richter, Manuela Friederike

AU - Bademci, Guney

AU - Rauch, Anita

AU - Fattahi, Zohreh

AU - Valentino, Maria Lucia

AU - Connolly, Anne M

AU - Bahr, Angela

AU - Viola, Laura

AU - Bergmann, Anke Katharina

AU - Rocha, Maria Eugenia

AU - Peart, LeShon

AU - Castro-Rojas, Derly Liseth

AU - Bültmann, Eva

AU - Khan, Suliman

AU - Giarrana, Miriam Liliana

AU - Teleanu, Raluca Ioana

AU - Gonzalez, Joanna Michelle

AU - Pini, Antonella

AU - Schädlich, Ines Sophie

AU - Vill, Katharina

AU - Brugger, Melanie

AU - Zuchner, Stephan

AU - Pinto, Andreia

AU - Donkervoort, Sandra

AU - Bivona, Stephanie Ann

AU - Riza, Anca

AU - Streata, Ioana

AU - Gläser, Dieter

AU - Baquero-Montoya, Carolina

AU - Garcia-Restrepo, Natalia

AU - Kotzaeridou, Urania

AU - Brunet, Theresa

AU - Epure, Diana Anamaria

AU - Bertoli-Avella, Aida

AU - Kariminejad, Ariana

AU - Tekin, Mustafa

AU - von Hardenberg, Sandra

AU - Bönnemann, Carsten G

AU - Stettner, Georg M

AU - Zanni, Ginevra

AU - Kayserili, Hülya

AU - Oflazer, Zehra Piraye

AU - Escande-Beillard, Nathalie

AU - Undiagnosed Diseases Network

N1 - © 2024. The Author(s).

PY - 2024/2/27

Y1 - 2024/2/27

N2 - SNURPORTIN-1, encoded by SNUPN, plays a central role in the nuclear import of spliceosomal small nuclear ribonucleoproteins. However, its physiological function remains unexplored. In this study, we investigate 18 children from 15 unrelated families who present with atypical muscular dystrophy and neurological defects. Nine hypomorphic SNUPN biallelic variants, predominantly clustered in the last coding exon, are ascertained to segregate with the disease. We demonstrate that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients' primary fibroblasts and CRISPR/Cas9-mediated mutant cell lines. Additionally, mutant nuclei exhibit defective spliceosomal maturation and breakdown of Cajal bodies. Transcriptome analyses reveal splicing and mRNA expression dysregulation, particularly in sarcolemmal components, causing disruption of cytoskeletal organization in mutant cells and patient muscle tissues. Our findings establish SNUPN deficiency as the genetic etiology of a previously unrecognized subtype of muscular dystrophy and provide robust evidence of the role of SPN1 for muscle homeostasis.

AB - SNURPORTIN-1, encoded by SNUPN, plays a central role in the nuclear import of spliceosomal small nuclear ribonucleoproteins. However, its physiological function remains unexplored. In this study, we investigate 18 children from 15 unrelated families who present with atypical muscular dystrophy and neurological defects. Nine hypomorphic SNUPN biallelic variants, predominantly clustered in the last coding exon, are ascertained to segregate with the disease. We demonstrate that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients' primary fibroblasts and CRISPR/Cas9-mediated mutant cell lines. Additionally, mutant nuclei exhibit defective spliceosomal maturation and breakdown of Cajal bodies. Transcriptome analyses reveal splicing and mRNA expression dysregulation, particularly in sarcolemmal components, causing disruption of cytoskeletal organization in mutant cells and patient muscle tissues. Our findings establish SNUPN deficiency as the genetic etiology of a previously unrecognized subtype of muscular dystrophy and provide robust evidence of the role of SPN1 for muscle homeostasis.

KW - Child

KW - Humans

KW - Muscular Dystrophies/genetics

KW - Ribonucleoproteins, Small Nuclear/metabolism

KW - RNA/metabolism

KW - RNA Splicing/genetics

KW - Spliceosomes/genetics

U2 - 10.1038/s41467-024-45933-5

DO - 10.1038/s41467-024-45933-5

M3 - SCORING: Journal article

C2 - 38413582

VL - 15

SP - 1758

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -