Loss of cardiac microRNA-mediated regulation leads to dilated cardiomyopathy and heart failure
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Jaenisch_Loss of.pdf
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Author(s)
Rao, Prakash K.
Chiang, H. Rosaria
Gupta, Sumeet
Bauer, Michael
Medvid, Rostislav
Reinhardt, Ferenc
Liao, Ronglih
Krieger, Monty
Jaenisch, Rudolf
Blelloch, Robert
Date Issued
August 2009
Journal
Circulation Research
Publisher
Ovid Technologies (Wolters Kluwer) -American Heart Association
Citation
Rao, P. K. et al. “Loss of Cardiac microRNA-Mediated Regulation Leads to Dilated Cardiomyopathy and Heart Failure.” Circulation Research 105.6 (2009): 585–594.
Version
Author's final manuscript
Abstract
Rationale: Heart failure is a deadly and devastating disease that places immense costs on an aging society. To develop therapies aimed at rescuing the failing heart, it is important to understand the molecular mechanisms underlying cardiomyocyte structure and function.
Objective: microRNAs are important regulators of gene expression, and we sought to define the global contributions made by microRNAs toward maintaining cardiomyocyte integrity.
Methods and Results: First, we performed deep sequencing analysis to catalog the miRNA population in the adult heart. Second, we genetically deleted, in cardiac myocytes, an essential component of the machinery that is required to generate miRNAs. Deep sequencing of miRNAs from the heart revealed the enrichment of a small number of microRNAs with one, miR-1, accounting for 40% of all microRNAs. Cardiomyocyte-specific deletion of dgcr8, a gene required for microRNA biogenesis, revealed a fully penetrant phenotype that begins with left ventricular malfunction progressing to a dilated cardiomyopathy and premature lethality.
Conclusions: These observations reveal a critical role for microRNAs in maintaining cardiac function in mature cardiomyocytes and raise the possibility that only a handful of microRNAs may ultimately be responsible for the dramatic cardiac phenotype seen in the absence of dgcr8.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1161/CIRCRESAHA.109.200451
