Airn Regulates Igf2bp2 Translation in Cardiomyocytes

Circ Res. 2018 May 11;122(10):1347-1353. doi: 10.1161/CIRCRESAHA.117.312215. Epub 2018 Feb 26.

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.

Keywords: RNA, long noncoding; RNA, untranslated; gene expression; myocytes, cardiac; transcriptome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Movement
  • Gene Expression Regulation
  • Mice
  • Myocardial Infarction / metabolism
  • Myocytes, Cardiac / metabolism*
  • Organ Specificity
  • Protein Binding
  • Protein Biosynthesis
  • RNA Interference
  • RNA Splicing
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology
  • RNA-Binding Proteins / biosynthesis*
  • RNA-Binding Proteins / genetics
  • Replication Protein A / metabolism

Substances

  • Air non-coding RNA, mouse
  • IGF2BP2 protein, mouse
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Replication Protein A
  • Rpa1 protein, mouse