Display options
Share it on

Front Mol Neurosci. 2017 Aug 21;10:259. doi: 10.3389/fnmol.2017.00259. eCollection 2017.

miRNA Enriched in Human Neuroblast Nuclei Bind the MAZ Transcription Factor and Their Precursors Contain the MAZ Consensus Motif.

Frontiers in molecular neuroscience

Belinda J Goldie, Chantel Fitzsimmons, Judith Weidenhofer, Joshua R Atkins, Dan O Wang, Murray J Cairns

Affiliations

  1. School of Biomedical Sciences and Pharmacy, The University of Newcastle, CallaghanNSW, Australia.
  2. Centre for Brain and Mental Health Research, Hunter Medical Research Institute, The University of Newcastle, CallaghanNSW, Australia.
  3. World Premier International Research Center - Institute for Integrated Cell-Material Sciences, Kyoto UniversityKyoto, Japan.
  4. The Keihanshin Consortium for Fostering the Next Generation of Global Leaders in ResearchKyoto, Japan.

PMID: 28878619 PMCID: PMC5573442 DOI: 10.3389/fnmol.2017.00259

Abstract

While the cytoplasmic function of microRNA (miRNA) as post-transcriptional regulators of mRNA has been the subject of significant research effort, their activity in the nucleus is less well characterized. Here we use a human neuronal cell model to show that some mature miRNA are preferentially enriched in the nucleus. These molecules were predominantly primate-specific and contained a sequence motif with homology to the consensus MAZ transcription factor binding element. Precursor miRNA containing this motif were shown to have affinity for MAZ protein in nuclear extract. We then used Ago1/2 RIP-Seq to explore nuclear miRNA-associated mRNA targets. Interestingly, the genes for Ago2-associated transcripts were also significantly enriched with MAZ binding sites and neural function, whereas Ago1-transcripts were associated with general metabolic processes and localized with SC35 spliceosomes. These findings suggest the MAZ transcription factor is associated with miRNA in the nucleus and may influence the regulation of neuronal development through Ago2-associated miRNA induced silencing complexes. The MAZ transcription factor may therefore be important for organizing higher order integration of transcriptional and post-transcriptional processes in primate neurons.

Keywords: Argonaute proteins; neuron differentiation; nuclear miRNA; primate-specific; regulation of gene expression; splicing

References

  1. Bioinformatics. 2015 Jan 15;31(2):166-9 - PubMed
  2. Proc Natl Acad Sci U S A. 2007 May 8;104(19):7957-62 - PubMed
  3. Nat Cell Biol. 2008 Aug;10(8):987-93 - PubMed
  4. Oncogene. 1997 Sep 4;15(10):1123-31 - PubMed
  5. Nucleic Acids Res. 2010 Mar;38(4):1086-97 - PubMed
  6. PLoS Genet. 2013;9(9):e1003821 - PubMed
  7. BMC Res Notes. 2012 Feb 13;5:92 - PubMed
  8. Nat Med. 2014 Jul;20(7):764-8 - PubMed
  9. Mol Cell. 2004 Jul 23;15(2):185-97 - PubMed
  10. Genome Biol. 2013 Apr 25;14(4):R36 - PubMed
  11. Aging (Albany NY). 2016 Feb;8(2):272-90 - PubMed
  12. Mol Cell Biol. 2009 Oct;29(20):5632-8 - PubMed
  13. Genes Dev. 2013 Feb 15;27(4):378-89 - PubMed
  14. RNA Biol. 2007 Jun;4(2):76-84 - PubMed
  15. Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):15622-9 - PubMed
  16. Biol Direct. 2011 Dec 02;6:61 - PubMed
  17. Biochem Biophys Res Commun. 2001 Sep 7;286(5):1087-97 - PubMed
  18. PLoS Biol. 2011 Dec;9(12):e1001214 - PubMed
  19. RNA. 2012 May;18(5):945-57 - PubMed
  20. RNA. 2011 Apr;17(4):675-86 - PubMed
  21. Int J Biochem Cell Biol. 2014 Sep;54:304-11 - PubMed
  22. Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21655-9 - PubMed
  23. Stat Appl Genet Mol Biol. 2004;3:Article3 - PubMed
  24. Bioinformatics. 2006 Dec 1;22(23):2926-33 - PubMed
  25. RNA. 2009 Sep;15(9):1705-15 - PubMed
  26. RNA. 2008 Jun;14(6):1244-53 - PubMed
  27. Nucleic Acids Res. 2007 Jul;35(Web Server issue):W169-75 - PubMed
  28. J Exp Med. 2010 Aug 30;207(9):1843-51 - PubMed
  29. Methods. 2006 Aug;39(4):356-62 - PubMed
  30. Nat Rev Genet. 2013 Jul;14(7):447-59 - PubMed
  31. J Biol Chem. 2011 Feb 11;286(6):4150-64 - PubMed
  32. FEBS Lett. 2011 Oct 3;585(19):2965-71 - PubMed
  33. J Biol Chem. 2010 Aug 20;285(34):25987-95 - PubMed
  34. Clin Cancer Res. 2014 Apr 1;20(7):1803-13 - PubMed
  35. Nat Genet. 2004 Nov;36(11):1174-80 - PubMed
  36. Mol Cell. 2010 Apr 9;38(1):67-77 - PubMed
  37. Nucleic Acids Res. 2015 Feb 18;43(3):1498-512 - PubMed
  38. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7452-6 - PubMed
  39. Comput Biol Chem. 2010 Aug;34(4):232-41 - PubMed
  40. Cell Cycle. 2009 Feb 1;8(3):345-56 - PubMed
  41. Front Mol Neurosci. 2013 Nov 26;6:43 - PubMed
  42. BMC Mol Biol. 2010 Dec 10;11:95 - PubMed
  43. Cell. 2007 Dec 14;131(6):1097-108 - PubMed
  44. EMBO J. 2011 Sep 30;30(21):4414-22 - PubMed
  45. Science. 2007 Jan 5;315(5808):97-100 - PubMed
  46. PLoS Genet. 2011 Oct;7(10):e1002330 - PubMed

Publication Types