The splicing factor hnRNPL demonstrates conserved myocardial regulation across species and is altered in heart failure

Isabelle Draper; Wanting Huang; Suchita Pande; Aaron Zou; Timothy D. Calamaras; Richard H. Choe; Ana Correia-Branco; Ariel L. Mei; Howard H. Chen; Hannah R. Littel; Mekala Gunasekaran; Natalya M. Wells; Christine C. Bruels; Audrey L. Daugherty; Matthew J. Wolf; Peter B. Kang; Vicky K. Yang; Donna K. Slonim; Mary C. Wallingford; Robert M. Blanton

doi:10.1002/1873-3468.15020

The splicing factor hnRNPL demonstrates conserved myocardial regulation across species and is altered in heart failure

Isabelle Draper, Wanting Huang, Suchita Pande, Aaron Zou, Timothy D. Calamaras, Richard H. Choe, Ana Correia-Branco, Ariel L. Mei, Howard H. Chen, Hannah R. Littel, Mekala Gunasekaran, Natalya M. Wells, Christine C. Bruels, Audrey L. Daugherty, Matthew J. Wolf, Peter B. Kang, Vicky K. Yang, Donna K. Slonim, Mary C. Wallingford, Robert M. Blanton

Research output: Contribution to journal › Article › peer-review

Abstract

Heart failure (HF) is highly prevalent. Mechanisms underlying HF remain incompletely understood. Splicing factors (SF), which control pre-mRNA alternative splicing, regulate cardiac structure and function. This study investigated regulation of the splicing factor heterogeneous nuclear ribonucleoprotein-L (hnRNPL) in the failing heart. hnRNPL protein increased in left ventricular tissue from mice with transaortic constriction-induced HF and from HF patients. In left ventricular tissue, hnRNPL was detected predominantly in nuclei. Knockdown of the hnRNPL homolog Smooth in Drosophila induced cardiomyopathy. Computational analysis of predicted mouse and human hnRNPL binding sites suggested hnRNPL-mediated alternative splicing of tropomyosin, which was confirmed in C2C12 myoblasts. These findings identify hnRNPL as a sensor of cardiac dysfunction and suggest that disturbances of hnRNPL affect alternative splicing in HF.

Original language	English (US)
Pages (from-to)	2670-2682
Number of pages	13
Journal	FEBS Letters
Volume	598
Issue number	21
DOIs	https://doi.org/10.1002/1873-3468.15020
State	Published - Nov 2024

Bibliographical note

Publisher Copyright:
© 2024 Federation of European Biochemical Societies.

Keywords

cardiomyopathy
heart failure
hnRNPL
mRNA splicing
splicing factors

PubMed: MeSH publication types

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1002/1873-3468.15020

Find It

Find It at U of M Libraries

Cite this

Draper, I., Huang, W., Pande, S., Zou, A., Calamaras, T. D., Choe, R. H., Correia-Branco, A., Mei, A. L., Chen, H. H., Littel, H. R., Gunasekaran, M., Wells, N. M., Bruels, C. C., Daugherty, A. L., Wolf, M. J., Kang, P. B., Yang, V. K., Slonim, D. K., Wallingford, M. C., & Blanton, R. M. (2024). The splicing factor hnRNPL demonstrates conserved myocardial regulation across species and is altered in heart failure. FEBS Letters, 598(21), 2670-2682. https://doi.org/10.1002/1873-3468.15020

Draper, I, Huang, W, Pande, S, Zou, A, Calamaras, TD, Choe, RH, Correia-Branco, A, Mei, AL, Chen, HH, Littel, HR, Gunasekaran, M, Wells, NM, Bruels, CC , Daugherty, AL, Wolf, MJ, Kang, PB, Yang, VK, Slonim, DK, Wallingford, MC & Blanton, RM 2024, 'The splicing factor hnRNPL demonstrates conserved myocardial regulation across species and is altered in heart failure', FEBS Letters, vol. 598, no. 21, pp. 2670-2682. https://doi.org/10.1002/1873-3468.15020

@article{dc556b3d69cd49b5b09c7d2a8d6f4bca,

title = "The splicing factor hnRNPL demonstrates conserved myocardial regulation across species and is altered in heart failure",

abstract = "Heart failure (HF) is highly prevalent. Mechanisms underlying HF remain incompletely understood. Splicing factors (SF), which control pre-mRNA alternative splicing, regulate cardiac structure and function. This study investigated regulation of the splicing factor heterogeneous nuclear ribonucleoprotein-L (hnRNPL) in the failing heart. hnRNPL protein increased in left ventricular tissue from mice with transaortic constriction-induced HF and from HF patients. In left ventricular tissue, hnRNPL was detected predominantly in nuclei. Knockdown of the hnRNPL homolog Smooth in Drosophila induced cardiomyopathy. Computational analysis of predicted mouse and human hnRNPL binding sites suggested hnRNPL-mediated alternative splicing of tropomyosin, which was confirmed in C2C12 myoblasts. These findings identify hnRNPL as a sensor of cardiac dysfunction and suggest that disturbances of hnRNPL affect alternative splicing in HF.",

keywords = "cardiomyopathy, heart failure, hnRNPL, mRNA splicing, splicing factors",

author = "Isabelle Draper and Wanting Huang and Suchita Pande and Aaron Zou and Calamaras, {Timothy D.} and Choe, {Richard H.} and Ana Correia-Branco and Mei, {Ariel L.} and Chen, {Howard H.} and Littel, {Hannah R.} and Mekala Gunasekaran and Wells, {Natalya M.} and Bruels, {Christine C.} and Daugherty, {Audrey L.} and Wolf, {Matthew J.} and Kang, {Peter B.} and Yang, {Vicky K.} and Slonim, {Donna K.} and Wallingford, {Mary C.} and Blanton, {Robert M.}",

note = "Publisher Copyright: {\textcopyright} 2024 Federation of European Biochemical Societies.",

year = "2024",

month = nov,

doi = "10.1002/1873-3468.15020",

language = "English (US)",

volume = "598",

pages = "2670--2682",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "John Wiley and Sons Inc.",

number = "21",

}

TY - JOUR

T1 - The splicing factor hnRNPL demonstrates conserved myocardial regulation across species and is altered in heart failure

AU - Draper, Isabelle

AU - Huang, Wanting

AU - Pande, Suchita

AU - Zou, Aaron

AU - Calamaras, Timothy D.

AU - Choe, Richard H.

AU - Correia-Branco, Ana

AU - Mei, Ariel L.

AU - Chen, Howard H.

AU - Littel, Hannah R.

AU - Gunasekaran, Mekala

AU - Wells, Natalya M.

AU - Bruels, Christine C.

AU - Daugherty, Audrey L.

AU - Wolf, Matthew J.

AU - Kang, Peter B.

AU - Yang, Vicky K.

AU - Slonim, Donna K.

AU - Wallingford, Mary C.

AU - Blanton, Robert M.

PY - 2024/11

Y1 - 2024/11

N2 - Heart failure (HF) is highly prevalent. Mechanisms underlying HF remain incompletely understood. Splicing factors (SF), which control pre-mRNA alternative splicing, regulate cardiac structure and function. This study investigated regulation of the splicing factor heterogeneous nuclear ribonucleoprotein-L (hnRNPL) in the failing heart. hnRNPL protein increased in left ventricular tissue from mice with transaortic constriction-induced HF and from HF patients. In left ventricular tissue, hnRNPL was detected predominantly in nuclei. Knockdown of the hnRNPL homolog Smooth in Drosophila induced cardiomyopathy. Computational analysis of predicted mouse and human hnRNPL binding sites suggested hnRNPL-mediated alternative splicing of tropomyosin, which was confirmed in C2C12 myoblasts. These findings identify hnRNPL as a sensor of cardiac dysfunction and suggest that disturbances of hnRNPL affect alternative splicing in HF.

AB - Heart failure (HF) is highly prevalent. Mechanisms underlying HF remain incompletely understood. Splicing factors (SF), which control pre-mRNA alternative splicing, regulate cardiac structure and function. This study investigated regulation of the splicing factor heterogeneous nuclear ribonucleoprotein-L (hnRNPL) in the failing heart. hnRNPL protein increased in left ventricular tissue from mice with transaortic constriction-induced HF and from HF patients. In left ventricular tissue, hnRNPL was detected predominantly in nuclei. Knockdown of the hnRNPL homolog Smooth in Drosophila induced cardiomyopathy. Computational analysis of predicted mouse and human hnRNPL binding sites suggested hnRNPL-mediated alternative splicing of tropomyosin, which was confirmed in C2C12 myoblasts. These findings identify hnRNPL as a sensor of cardiac dysfunction and suggest that disturbances of hnRNPL affect alternative splicing in HF.

KW - cardiomyopathy

KW - heart failure

KW - hnRNPL

KW - mRNA splicing

KW - splicing factors

UR - http://www.scopus.com/inward/record.url?scp=85204496728&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85204496728&partnerID=8YFLogxK

U2 - 10.1002/1873-3468.15020

DO - 10.1002/1873-3468.15020

M3 - Article

C2 - 39300280

AN - SCOPUS:85204496728

SN - 0014-5793

VL - 598

SP - 2670

EP - 2682

JO - FEBS Letters

JF - FEBS Letters

IS - 21

ER -

The splicing factor hnRNPL demonstrates conserved myocardial regulation across species and is altered in heart failure

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this