<i>Airn</i> Regulates Igf2bp2 Translation in Cardiomyocytes.

Abstract

Increasing evidence indicates the presence of lncRNAs in various cell types. <i>Airn</i> is an imprinting gene transcribed from the paternal chromosome. It is in antisense orientation to the imprinted, but maternally derived, <i>Igf2r</i> gene, on which <i>Airn</i> exerts its regulation in <i>cis</i>. Although <i>Airn</i> is highly expressed in the heart, functions aside from imprinting remain unknown. Here, we studied the functions of <i>Airn</i> in the heart, especially cardiomyocytes. Silencing of <i>Airn</i> 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 <i>Airn</i> 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 <i>Airn</i> binds to Igf2bp2 to control the translation of several genes. Moreover, silencing of <i>Airn</i> caused less binding of Igf2bp2 to other mRNAs and reduced translation of Igf2bp2 protein. Our study uncovers a new function of <i>Airn</i> and demonstrates that <i>Airn</i> is important for the physiology of cardiomyocytes.