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The regulation of mitochondrial biogenesis is under the control of nuclear genes including the master Mitochondrial Transcription Factor A (TFAM). Recent evidence suggests that the expression of TFAM is regulated by microRNAs (miRNAs) in various cellular contexts. Here, we show that hsa-miR-155-5p, a prominent miRNA encoded in chromosome 21, controls the expression of TFAM at the post-transcriptional level. In human fibroblasts derived from a diploid donor, downregulation of TFAM by hsa-miR-155-5p decreased mitochondrial DNA (mtDNA) content. In contrast, downregulation of TFAM by hsa-miR-155-5p did not decrease mtDNA content in fibroblasts derived from a donor with Down syndrome (DS, trisomy 21). In line, downregulation of mitochondrial TFAM levels through hsa-miR-155-5p decreased mitochondrial mass in diploid fibroblasts but not in trisomic cells. Due to the prevalence of mitochondrial dysfunction and cardiac abnormalities in subjects with DS, we examined the presence of potential associations between hsa-miR-155-5p and TFAM expression in heart samples from donors with and without DS. There were significant negative associations between hsa-miR-155-5p and TFAM expression in heart samples from donors with and without DS. These results suggest that regulation of TFAM by hsa-miR-155-5p impacts mitochondrial biogenesis in the diploid setting but not in the DS setting.

Titel:	Chromosome 21-derived hsa-miR-155-5p regulates mitochondrial biogenesis by targeting Mitochondrial Transcription Factor A (TFAM).
Autor/in / Beteiligte Person:	Quiñones-Lombraña, A ; Blanco, JG
Zeitschrift:	Biochimica et biophysica acta, Jg. 1852 (2015-07-01), Heft 7, S. 1420-7
Veröffentlichung:	Amsterdam : Elsevier Pub. Co., 2015
Medientyp:	academicJournal
ISSN:	0006-3002 (print)
DOI:	10.1016/j.bbadis.2015.04.004
Schlagwort:	Animals CHO Cells Case-Control Studies Cells, Cultured Chromosomes, Human, Pair 21 genetics Cricetinae Cricetulus DNA, Mitochondrial genetics DNA-Binding Proteins metabolism Down Syndrome genetics Fibroblasts metabolism Humans MicroRNAs metabolism Mitochondrial Proteins metabolism Myocytes, Cardiac metabolism Ploidies Transcription Factors metabolism DNA-Binding Proteins genetics MicroRNAs genetics Mitochondrial Proteins genetics Mitochondrial Turnover Transcription Factors genetics
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural Language: English [Biochim Biophys Acta] 2015 Jul; Vol. 1852 (7), pp. 1420-7. <i>Date of Electronic Publication: </i>2015 Apr 11. MeSH Terms: Mitochondrial Turnover* ; DNA-Binding Proteins / genetics ; MicroRNAs / genetics ; Mitochondrial Proteins / genetics ; Transcription Factors / genetics ; Animals ; CHO Cells ; Case-Control Studies ; Cells, Cultured ; Chromosomes, Human, Pair 21 / genetics ; Cricetinae ; Cricetulus ; DNA, Mitochondrial / genetics ; DNA-Binding Proteins / metabolism ; Down Syndrome / genetics ; Fibroblasts / metabolism ; Humans ; MicroRNAs / metabolism ; Mitochondrial Proteins / metabolism ; Myocytes, Cardiac / metabolism ; Ploidies ; Transcription Factors / metabolism References: Curr Protoc Cell Biol. 2010 Mar;Chapter 4:Unit 4.25.1-21. (PMID: 20235105) ; Annu Rev Biochem. 2007;76:679-99. (PMID: 17408359) ; Nucleic Acids Res. 2001 Sep 1;29(17):3657-63. (PMID: 11522837) ; Oncol Rep. 2013 Nov;30(5):2105-10. (PMID: 24002170) ; Neurosci Biobehav Rev. 2014 Oct;46 Pt 2:202-17. (PMID: 24548784) ; Curr Gerontol Geriatr Res. 2012;2012:383170. (PMID: 22611387) ; Hum Mol Genet. 2004 May 1;13(9):935-44. (PMID: 15016765) ; Mol Cell. 2012 Dec 14;48(5):760-70. (PMID: 23142080) ; Mol Genet Metab. 2011 Mar;102(3):378-82. (PMID: 21195648) ; Drug Metab Dispos. 2010 Dec;38(12):2096-9. (PMID: 20729274) ; Nat Rev Genet. 2008 Feb;9(2):102-14. (PMID: 18197166) ; Nature. 2014 Apr 17;508(7496):345-50. (PMID: 24740065) ; Mitochondrial DNA A DNA MappSeq Anal. 2016;27(2):896-903. (PMID: 24938108) ; Nat Protoc. 2008;3(6):1101-8. (PMID: 18546601) ; Am J Physiol Endocrinol Metab. 2012 Dec 15;303(12):E1419-27. (PMID: 23047984) ; RNA. 2004 Oct;10(10):1507-17. (PMID: 15383676) ; Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18410-5. (PMID: 20930118) ; Biochim Biophys Acta. 2009 Jun;1792(6):497-505. (PMID: 19268705) ; Pharm Res. 2014 Jul;31(7):1644-55. (PMID: 24562808) ; Clin Chem. 2009 Apr;55(4):611-22. (PMID: 19246619) ; J Alzheimers Dis. 2010;20 Suppl 2:S293-310. (PMID: 20463402) ; DNA Cell Biol. 2014 May;33(5):291-300. (PMID: 24684598) ; Dev Cell. 2002 Mar;2(3):255-6. (PMID: 11879629) ; Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1604-9. (PMID: 17242365) ; Hum Mol Genet. 2013 Mar 15;22(6):1218-32. (PMID: 23257287) ; Circ Res. 2012 Aug 3;111(4):415-25. (PMID: 22715471) ; Biogerontology. 2010 Aug;11(4):401-19. (PMID: 20237955) ; Nat Commun. 2013;4:1769. (PMID: 23612310) ; FEBS Lett. 2007 Feb 6;581(3):521-5. (PMID: 17250829) ; Nucleic Acids Res. 2006;34(20):5815-28. (PMID: 17062618) ; Bioessays. 2002 Aug;24(8):681-4. (PMID: 12210526) ; Am J Hum Genet. 2007 Aug;81(2):405-13. (PMID: 17668390) Grant Information: R01 GM073646 United States GM NIGMS NIH HHS; R03 HD076055 United States HD NICHD NIH HHS; R01GM073646 United States GM NIGMS NIH HHS; R03HD076055 United States HD NICHD NIH HHS Contributed Indexing: Keywords: Down syndrome; Hsa-miR-155-5p; Mitochondrial biogenesis; TFAM Substance Nomenclature: 0 (DNA, Mitochondrial) ; 0 (DNA-Binding Proteins) ; 0 (MIRN155 microRNA, human) ; 0 (MicroRNAs) ; 0 (Mitochondrial Proteins) ; 0 (TFAM protein, human) ; 0 (Transcription Factors) Entry Date(s): Date Created: 20150415 Date Completed: 20150827 Latest Revision: 20181113 Update Code: 20231215 PubMed Central ID: PMC4433801

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Chromosome 21-derived hsa-miR-155-5p regulates mitochondrial biogenesis by targeting Mitochondrial Transcription Factor A (TFAM).