title: Dynamic recruitment of microRNAs to their mRNA targets in the regenerating liver.
abstract: BACKGROUND
  Validation of physiologic miRNA targets has been met with significant challenges. We employed HITS-CLIP to identify which miRNAs participate in liver regeneration, and to identify their target mRNAs.
  
  
  RESULTS
  miRNA recruitment to the RISC is highly dynamic, changing more than five-fold for several miRNAs. miRNA recruitment to the RISC did not correlate with changes in overall miRNA expression for these dynamically recruited miRNAs, emphasizing the necessity to determine miRNA recruitment to the RISC in order to fully assess the impact of miRNA regulation. We incorporated RNA-seq quantification of total mRNA to identify expression-weighted Ago footprints, and developed a microRNA regulatory element (MRE) prediction algorithm that represents a greater than 20-fold refinement over computational methods alone. These high confidence MREs were used to generate candidate 'competing endogenous RNA' (ceRNA) networks.
  
  
  CONCLUSIONS
  HITS-CLIP analysis provide novel insights into global miRNA:mRNA relationships in the regenerating liver.
authors.affiliation: Department of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schug
authors.forename: Lindsay B
authors.initials: LB
authors.lastname: McKenna
authors.forename: Gabriel
authors.initials: G
authors.lastname: Walton
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hand
authors.forename: Sarmistha
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Kow
authors.initials: K
authors.lastname: Essuman
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Shi
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Karen
authors.initials: K
authors.lastname: Markley
authors.forename: Momo
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Vasumathi
authors.initials: V
authors.lastname: Kameswaran
authors.forename: Anastassios
authors.initials: A
authors.lastname: Vourekas
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Friedman
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
authors.forename: Linda E
authors.initials: LE
authors.lastname: Greenbaum
mesh_terms: D000818:Animals; D002453:Cell Cycle; D053263:Gene Regulatory Networks; D047468:Immunoprecipitation / Q000379:methods; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000235:genetics
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D034743:RNA-Induced Silencing Complex