title: MicroRNAs function as cis- and trans-acting modulators of peripheral circadian clocks.
abstract: Based on their extracellular expression and targeting of the clock gene Bmal1, miR-142-3p and miR-494 were analyzed for evidence of vesicle-mediated communication between cells and intracellular functional activity. Our studies demonstrate that: miR-142-3p+miR-494 overexpression decreases endogenous BMAL1 levels, increases the period of Per2 oscillations, and increases extracellular miR-142-3p/miR-494 abundance in conditioned medium; miRNA-enriched medium increases intracellular expression of miR-142-3p and represses Bmal1 3'-UTR activity in naïve cells; and inhibitors of vesicular trafficking modulate intercellular communication of these miRNAs and ensemble Per2 rhythms. Thus, miR-142-3p and miR-494 may function as cis- and trans-acting signals contributing to local temporal coordination of cell-autonomous circadian clocks.
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX, USA; Center for Biological Clocks Research, Texas A&M University, College Station, TX, USA.
authors.forename: Vikram R
authors.initials: VR
authors.lastname: Shende
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX, USA; Center for Biological Clocks Research, Texas A&M University, College Station, TX, USA.
authors.forename: Sam-Moon
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, College of Medicine, Bryan, TX, USA.
authors.forename: Nichole
authors.initials: N
authors.lastname: Neuendorff
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX, USA; Center for Biological Clocks Research, Texas A&M University, College Station, TX, USA; Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, College of Medicine, Bryan, TX, USA. Electronic address: dearnest@medicine.tamhsc.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Earnest
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics; D000818:Animals; D002450:Cell Communication; D057906:Circadian Clocks / Q000235:genetics*; D004705:Endocytosis; D005089:Exocytosis; D005110:Extracellular Space / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D041681:NIH 3T3 Cells
chemical_list: D056930:ARNTL Transcription Factors; C555159:MIRN142 microRNA, human; C547168:MIRN494 microRNA, human; D035683:MicroRNAs
keywords: 3′-UTR; Circadian; Clock; E-box; Oscillation; Pacemaker; Period 1; Period 2; miRNA-recognition element