title: miR-135A regulates preimplantation embryo development through down-regulation of E3 Ubiquitin Ligase Seven In Absentia Homolog 1A (SIAH1A) expression.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are small non-coding RNA molecules capable of regulating transcription and translation. Previously, a cluster of miRNAs that are specifically expressed in mouse zygotes but not in oocytes or other preimplantation stages embryos are identified by multiplex real-time polymerase chain reaction-based miRNA profiling. The functional role of one of these zygote-specific miRNAs, miR-135a, in preimplantation embryo development was investigated.
  
  
  RESULTS
  Microinjection of miR-135a inhibitor suppressed first cell cleavage in more than 30% of the zygotes. Bioinformatics analysis identified E3 Ubiquitin Ligase Seven In Absentia Homolog 1A (Siah1a) as a predicted target of miR-135a. Western blotting and 3'UTR luciferase functional assays demonstrated that miR-135a down-regulated the expression of Siah1 in HeLa cells and in mouse zygotes. Siah1a was expressed in preimplantation embryos and its expression pattern negatively correlated with that of miR-135a. Co-injection of Siah1a-specific antibody with miR-135a inhibitor partially nullified the effect of miR-135a inhibition. Proteasome inhibition by MG-132 revealed that miR-135a regulated proteasomal degradation and potentially controlled the expression of chemokinesin DNA binding protein (Kid).
  
  
  CONCLUSIONS
  The present study demonstrated for the first time that zygotic specific miRNA modulates the first cell cleavage through regulating expression of Siah1a.
authors: Department of Obstetrics and Gynaecology, The University of Hong Kong, Pokfulam, Hong Kong, People's Republic of China.
authors: Ronald T K
authors: RT
authors: Pang
authors: Wei-Min
authors: WM
authors: Liu
authors: Carmen O N
authors: CO
authors: Leung
authors: Tian-Min
authors: TM
authors: Ye
authors: Peter C K
authors: PC
authors: Kwan
authors: Kai-Fai
authors: KF
authors: Lee
authors: William S B
authors: WS
authors: Yeung
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008845:Microinjections; D009865:Oocytes / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D021381:Protein Transport; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D059748:Proteolysis; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; C549289:Mirn135 microRNA, mouse; D011506:Proteins; C484442:Siah1a protein, mouse; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; C527520:Kid protein, mouse; D016547:Kinesins