TY - JOUR
T1 - Airn regulates IGF2BP2 translation in cardiomyocytes
AU - Hosen, Mohammed Rabiul
AU - Militello, Giuseppe
AU - Weirick, Tyler
AU - Ponomareva, Yuliya
AU - Dassanayaka, Sujith
AU - Moore, Joseph B.
AU - Döring, Claudia
AU - Wysoczynski, Marcin
AU - Jones, Steven P.
AU - Dimmeler, Stefanie
AU - Uchida, Shizuka
PY - 2018/5
Y1 - 2018/5
N2 - 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.
AB - 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.
KW - Cardiac
KW - Gene expression
KW - Long noncoding
KW - Myocytes
KW - RNA
KW - Transcriptome
KW - Untranslated
UR - http://www.scopus.com/inward/record.url?scp=85048888434&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.117.312215
DO - 10.1161/CIRCRESAHA.117.312215
M3 - Journal article
C2 - 29483092
AN - SCOPUS:85048888434
SN - 0009-7330
VL - 122
SP - 1347
EP - 1353
JO - Circulation Research
JF - Circulation Research
IS - 10
ER -