title: Loss of cardiac microRNA-mediated regulation leads to dilated cardiomyopathy and heart failure.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors.forename: Prakash K
authors.initials: PK
authors.lastname: Rao
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Toyama
authors.forename: H Rosaria
authors.initials: HR
authors.lastname: Chiang
authors.forename: Sumeet
authors.initials: S
authors.lastname: Gupta
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
authors.forename: Rostislav
authors.initials: R
authors.lastname: Medvid
authors.forename: Ferenc
authors.initials: F
authors.lastname: Reinhardt
authors.forename: Ronglih
authors.initials: R
authors.lastname: Liao
authors.forename: Monty
authors.initials: M
authors.lastname: Krieger
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
authors.forename: Harvey F
authors.initials: HF
authors.lastname: Lodish
authors.forename: Robert
authors.initials: R
authors.lastname: Blelloch
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins
chemical_list: C474044:Dgcr8 protein, mouse; D035683:MicroRNAs; C517731:Mirn1 microRNA, mouse; D011506:Proteins; D016601:RNA-Binding Proteins
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