The mechanical regulation of RNA binding protein hnRNPC in the failing heart

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F22%3A00077730" target="_blank" >RIV/00159816:_____/22:00077730 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/22:00128822 RIV/00209775:_____/22:N0000018

Výsledek na webu

<a href="https://www.science.org/doi/10.1126/scitranslmed.abo5715#core-collateral-purchase-access" target="_blank" >https://www.science.org/doi/10.1126/scitranslmed.abo5715#core-collateral-purchase-access</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1126/scitranslmed.abo5715" target="_blank" >10.1126/scitranslmed.abo5715</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The mechanical regulation of RNA binding protein hnRNPC in the failing heart

Popis výsledku v původním jazyce

Cardiac pathologies are characterized by intense remodeling of the extracellular matrix (ECM) that eventually leads to heart failure. Cardiomyocytes respond to the ensuing biomechanical stress by reexpressing fetal contractile proteins via transcriptional and posttranscriptional processes, such as alternative splicing (AS). Here, we demonstrate that the heterogeneous nuclear ribonucleoprotein C (hnRNPC) is up-regulated and relocates to the sarcomeric Z-disc upon ECM pathological remodeling. We show that this is an active site of localized translation, where the ribonucleoprotein associates with the translation machinery. Alterations in hnRNPC expression, phosphorylation, and localization can be mechanically determined and affect the AS of mRNAs involved in mechanotransduction and cardiovascular diseases, including Hippo pathway effector Yes-associated protein 1. We propose that cardiac ECM remodeling serves as a switch in RNA metabolism by affecting an associated regulatory protein of the spliceosome apparatus. These findings offer new insights on the mechanism of mRNA homeostatic mechanoregulation in pathological conditions.

Název v anglickém jazyce

The mechanical regulation of RNA binding protein hnRNPC in the failing heart

Popis výsledku anglicky

Cardiac pathologies are characterized by intense remodeling of the extracellular matrix (ECM) that eventually leads to heart failure. Cardiomyocytes respond to the ensuing biomechanical stress by reexpressing fetal contractile proteins via transcriptional and posttranscriptional processes, such as alternative splicing (AS). Here, we demonstrate that the heterogeneous nuclear ribonucleoprotein C (hnRNPC) is up-regulated and relocates to the sarcomeric Z-disc upon ECM pathological remodeling. We show that this is an active site of localized translation, where the ribonucleoprotein associates with the translation machinery. Alterations in hnRNPC expression, phosphorylation, and localization can be mechanically determined and affect the AS of mRNAs involved in mechanotransduction and cardiovascular diseases, including Hippo pathway effector Yes-associated protein 1. We propose that cardiac ECM remodeling serves as a switch in RNA metabolism by affecting an associated regulatory protein of the spliceosome apparatus. These findings offer new insights on the mechanism of mRNA homeostatic mechanoregulation in pathological conditions.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Science Translational Medicine

ISSN

1946-6234

e-ISSN

1946-6242

Svazek periodika

14

Číslo periodika v rámci svazku

672

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

nestrankovano

Kód UT WoS článku

000892365400001

EID výsledku v databázi Scopus

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