Loss of Cardiac Splicing Regulator RBM20 Is Associated With Early-Onset Atrial Fibrillation

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Loss of Cardiac Splicing Regulator RBM20 Is Associated With Early-Onset Atrial Fibrillation. / Vad, Oliver B.; Angeli, Elisavet; Liss, Martin; Ahlberg, Gustav; Andreasen, Laura; Christophersen, Ingrid E.; Hansen, Camilla C.; Møller, Sophie; Hellsten, Ylva; Haunsoe, Stig; Tveit, Arnljot; Svendsen, Jesper H.; Gotthardt, Michael; Lundegaard, Pia R.; Olesen, Morten S.

I: JACC: Basic to Translational Science, Bind 9, Nr. 2, 2024, s. 163-180.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Vad, OB, Angeli, E, Liss, M, Ahlberg, G, Andreasen, L, Christophersen, IE, Hansen, CC, Møller, S, Hellsten, Y, Haunsoe, S, Tveit, A, Svendsen, JH, Gotthardt, M, Lundegaard, PR & Olesen, MS 2024, 'Loss of Cardiac Splicing Regulator RBM20 Is Associated With Early-Onset Atrial Fibrillation', JACC: Basic to Translational Science, bind 9, nr. 2, s. 163-180. https://doi.org/10.1016/j.jacbts.2023.08.008

APA

Vad, O. B., Angeli, E., Liss, M., Ahlberg, G., Andreasen, L., Christophersen, I. E., Hansen, C. C., Møller, S., Hellsten, Y., Haunsoe, S., Tveit, A., Svendsen, J. H., Gotthardt, M., Lundegaard, P. R., & Olesen, M. S. (2024). Loss of Cardiac Splicing Regulator RBM20 Is Associated With Early-Onset Atrial Fibrillation. JACC: Basic to Translational Science, 9(2), 163-180. https://doi.org/10.1016/j.jacbts.2023.08.008

Vancouver

Vad OB, Angeli E, Liss M, Ahlberg G, Andreasen L, Christophersen IE o.a. Loss of Cardiac Splicing Regulator RBM20 Is Associated With Early-Onset Atrial Fibrillation. JACC: Basic to Translational Science. 2024;9(2):163-180. https://doi.org/10.1016/j.jacbts.2023.08.008

Author

Vad, Oliver B. ; Angeli, Elisavet ; Liss, Martin ; Ahlberg, Gustav ; Andreasen, Laura ; Christophersen, Ingrid E. ; Hansen, Camilla C. ; Møller, Sophie ; Hellsten, Ylva ; Haunsoe, Stig ; Tveit, Arnljot ; Svendsen, Jesper H. ; Gotthardt, Michael ; Lundegaard, Pia R. ; Olesen, Morten S. / Loss of Cardiac Splicing Regulator RBM20 Is Associated With Early-Onset Atrial Fibrillation. I: JACC: Basic to Translational Science. 2024 ; Bind 9, Nr. 2. s. 163-180.

Bibtex

@article{14fd93daeecd4766b5f3effe2f0ee1fe,

title = "Loss of Cardiac Splicing Regulator RBM20 Is Associated With Early-Onset Atrial Fibrillation",

abstract = "We showed an association between atrial fibrillation and rare loss-of-function (LOF) variants in the cardiac splicing regulator RBM20 in 2 independent cohorts. In a rat model with loss of RBM20, we demonstrated altered splicing of sarcomere genes (NEXN, TTN, TPM1, MYOM1, and LDB3), and differential expression in key cardiac genes. We identified altered sarcomere and mitochondrial structure on electron microscopy imaging and found compromised mitochondrial function. Finally, we demonstrated that 3 novel LOF variants in RBM20, identified in patients with atrial fibrillation, lead to significantly reduced splicing activity. Our results implicate alternative splicing as a novel proarrhythmic mechanism in the atria.",

keywords = "alternative splicing, atrial cardiomyopathy, atrial fibrillation, genetics, RBM20",

author = "Vad, {Oliver B.} and Elisavet Angeli and Martin Liss and Gustav Ahlberg and Laura Andreasen and Christophersen, {Ingrid E.} and Hansen, {Camilla C.} and Sophie M{\o}ller and Ylva Hellsten and Stig Haunsoe and Arnljot Tveit and Svendsen, {Jesper H.} and Michael Gotthardt and Lundegaard, {Pia R.} and Olesen, {Morten S.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

doi = "10.1016/j.jacbts.2023.08.008",

language = "English",

volume = "9",

pages = "163--180",

journal = "JACC: Basic to Translational Science",

issn = "2452-302X",

publisher = "Elsevier",

number = "2",

}

RIS

TY - JOUR

T1 - Loss of Cardiac Splicing Regulator RBM20 Is Associated With Early-Onset Atrial Fibrillation

AU - Vad, Oliver B.

AU - Angeli, Elisavet

AU - Liss, Martin

AU - Ahlberg, Gustav

AU - Andreasen, Laura

AU - Christophersen, Ingrid E.

AU - Hansen, Camilla C.

AU - Møller, Sophie

AU - Hellsten, Ylva

AU - Haunsoe, Stig

AU - Tveit, Arnljot

AU - Svendsen, Jesper H.

AU - Gotthardt, Michael

AU - Lundegaard, Pia R.

AU - Olesen, Morten S.

PY - 2024

Y1 - 2024

N2 - We showed an association between atrial fibrillation and rare loss-of-function (LOF) variants in the cardiac splicing regulator RBM20 in 2 independent cohorts. In a rat model with loss of RBM20, we demonstrated altered splicing of sarcomere genes (NEXN, TTN, TPM1, MYOM1, and LDB3), and differential expression in key cardiac genes. We identified altered sarcomere and mitochondrial structure on electron microscopy imaging and found compromised mitochondrial function. Finally, we demonstrated that 3 novel LOF variants in RBM20, identified in patients with atrial fibrillation, lead to significantly reduced splicing activity. Our results implicate alternative splicing as a novel proarrhythmic mechanism in the atria.

AB - We showed an association between atrial fibrillation and rare loss-of-function (LOF) variants in the cardiac splicing regulator RBM20 in 2 independent cohorts. In a rat model with loss of RBM20, we demonstrated altered splicing of sarcomere genes (NEXN, TTN, TPM1, MYOM1, and LDB3), and differential expression in key cardiac genes. We identified altered sarcomere and mitochondrial structure on electron microscopy imaging and found compromised mitochondrial function. Finally, we demonstrated that 3 novel LOF variants in RBM20, identified in patients with atrial fibrillation, lead to significantly reduced splicing activity. Our results implicate alternative splicing as a novel proarrhythmic mechanism in the atria.

KW - alternative splicing

KW - atrial cardiomyopathy

KW - atrial fibrillation

KW - genetics

KW - RBM20

U2 - 10.1016/j.jacbts.2023.08.008

DO - 10.1016/j.jacbts.2023.08.008

M3 - Journal article

AN - SCOPUS:85184814509

VL - 9

SP - 163

EP - 180

JO - JACC: Basic to Translational Science

JF - JACC: Basic to Translational Science

SN - 2452-302X

IS - 2

ER -

ID: 382904312

Institut for Idræt og Ernæring