Airn Regulates Igf2bp2 Translation in Cardiomyocytes. Issue 10 (11th May 2018)

• Record Type: Journal Article
• Authors: Hosen, Mohammed Rabiul; Militello, Giuseppe; Weirick, Tyler; Ponomareva, Yuliya; Dassanayaka, Sujith; Moore, Joseph B.; Döring, Claudia; Wysoczynski, Marcin; Jones, Steven P.; Dimmeler, Stefanie; Uchida, Shizuka
• Is Part Of: Circulation research. Volume 122:Issue 10(2018)
• Publication Date: 2018-05-11
• Subjects: gene expression -- myocytes, cardiac -- RNA, long noncoding -- RNA, untranslated -- transcriptome; Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.117.312215
• Languages: English
• ISSNs: 0009-7330

Abstract

Abstract : Rationale: : Increasing evidence indicates the presence of lncRNAs in various cell types. Airn is an imprinting gene transcribed from the paternal chromosome. It is in antisense orientation to the imprinted, but maternally derived, Igf2r gene, on which Airn exerts its regulation in cis . Although Airn is highly expressed in the heart, functions aside from imprinting remain unknown. Objective: : Here, we studied the functions of Airn in the heart, especially cardiomyocytes. Methods and Results: : Silencing of Airn via siRNAs augmented cell death, vulnerability to cellular stress, and reduced cell migration. To find the cause of such phenotypes, the potential binding partners of Airn were identified via RNA pull-down followed by mass spectrometry, which indicated Igf2bp2 (insulin-like growth factor 2 mRNA-binding protein 2) and Rpa1 (replication protein A1) as potential binding partners. Further experiments showed that Airn binds to Igf2bp2 to control the translation of several genes. Moreover, silencing of Airn caused less binding of Igf2bp2 to other mRNAs and reduced translation of Igf2bp2 protein. Conclusions: : Our study uncovers a new function of Airn and demonstrates that Airn is important for the physiology of cardiomyocytes. Abstract : Supplemental Digital Content is available in the text.