RNA binding protein IGF2BP2 expression is induced by stress in the heart and mediates dilated cardiomyopathy

Miriam Krumbein, Froma Oberman, Yuval Cinnamon, Mordechai Golomb, Dalit May, Gilad Vainer, Vitali Belzer, Karen Meir, Irina Fridman, Johannes Haybaeck, Gerhard Poelzl, Izhak Kehat, Ronen Beeri, Sonja M. Kessler*, Joel K. Yisraeli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The IGF2BP family of RNA binding proteins consists of three paralogs that regulate intracellular RNA localization, RNA stability, and translational control. Although IGF2BP1 and 3 are oncofetal proteins, IGF2BP2 expression is maintained in many tissues, including the heart, into adulthood. IGF2BP2 is upregulated in cardiomyocytes during cardiac stress and remodeling and returns to normal levels in recovering hearts. We wondered whether IGF2BP2 might play an adaptive role during cardiac stress and recovery. Enhanced expression of an IGF2BP2 transgene in a conditional, inducible mouse line leads to dilated cardiomyopathy (DCM) and death within 3-4 weeks in newborn or adult hearts. Downregulation of the transgene after 2 weeks, however, rescues these mice, with complete recovery by 12 weeks. Hearts overexpressing IGF2BP2 downregulate sarcomeric and mitochondrial proteins and have fragmented mitochondria and elongated, thinner sarcomeres. IGF2BP2 is also upregulated in DCM or myocardial infarction patients. These results suggest that IGF2BP2 may be an attractive target for therapeutic intervention in cardiomyopathies.

Original languageAmerican English
Article number1229
JournalCommunications Biology
Volume6
Issue number1
DOIs
StatePublished - 5 Dec 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

Fingerprint

Dive into the research topics of 'RNA binding protein IGF2BP2 expression is induced by stress in the heart and mediates dilated cardiomyopathy'. Together they form a unique fingerprint.

Cite this