title: Knockdown of PU.1 AS lncRNA inhibits adipogenesis through enhancing PU.1 mRNA translation.
abstract: PU.1 is an Ets family transcription factor involved in the myelo-lymphoid differentiation. We have previously demonstrated that PU.1 is also expressed in the adipocyte lineage. However, the expression levels of PU.1 mRNA and protein in preadipocytes do not match the levels in mature adipocytes. PU.1 mRNA level is higher in preadipocytes, whereas its protein is expressed in the adipocytes but not in the preadipocytes. The underlying mechanism remains elusive. Here, we find that miR-155 knockdown or overexpression has no effect on the levels of PU.1 mRNA and protein in preadipocytes or adipocytes. MiR-155 regulates adipogenesis not through PU.1, but via C/EBPβ which is another target of miR-155. We also checked the expression levels of PU.1 mRNA and antisense long non-coding RNA (AS lncRNA). Interestingly, compared with the level of PU.1 mRNA, the level of PU.1 AS lncRNA is much higher in preadipocytes, whereas it is opposite in the adipocytes. We further discover that PU.1 AS lncRNA binds to its mRNA forming an mRNA/AS lncRNA compound. The knockdown of PU.1 AS by siRNA inhibits adipogenesis and promotes PU.1 protein expression in both preadipocytes and adipocytes. Furthermore, the repression of PU.1 AS decreases the expression and secretion of adiponectin. We also find that the effect of retroviral-mediated PU.1 AS knockdown on adipogenesis is consistent with that of PU.1 AS knockdown by siRNA. Taken together, our results suggest that PU.1 AS lncRNA promotes adipogenesis through preventing PU.1 mRNA translation via binding to PU.1 mRNA to form mRNA/AS lncRNA duplex in preadipocytes.
authors.affiliation: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China; Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, 77030.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Pang
authors.forename: Li-Gen
authors.initials: LG
authors.lastname: Lin
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiong
authors.forename: Ning
authors.initials: N
authors.lastname: Wei
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Qing-Wu
authors.initials: QW
authors.lastname: Shen
authors.forename: Gong-She
authors.initials: GS
authors.lastname: Yang
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D052242:Adiponectin; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C532623:Mirn155 microRNA, mouse
keywords: ADIPOCYTE; ADIPOGENESIS; ANTISENSE lncRNA; PU.1; miR-155