MIR34A

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MIR34A
Identifiers
AliasesMIR34A, MIRN34A, miRNA34A, mir-34, mir-34a, microRNA 34a, MIRN34 microRNA, human
External IDsOMIM: 611172 GeneCards: MIR34A
Orthologs
SpeciesHumanMouse
Entrez

407040

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Ensembl

ENSG00000284357

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UniProt

n
a

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RefSeq (mRNA)

n/a

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RefSeq (protein)

n/a

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Location (UCSC)Chr 1: 9.15 – 9.15 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

MicroRNA 34a (miR-34a) is a MicroRNA that in humans is encoded by the MIR34A gene.[3]

Function

microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding.

The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products.

The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop.

Repair of DNA damage

Expression of miR-34A is markedly up-regulated in hematopoietic stem cells (HSCs) from mice subjected to ionizing radiation.[4] HSCs that are deficient in miR-34A have decreased expression of genes involved in the DNA repair processes of homologous recombination and non-homologous end joining.[4] These and other findings demonstrate that miR-34A contributes to the survival of HSCs after irradiation.[4]

Clinical relevance

miR-34a suppresses the gene expression of the NAMPT gene which encodes the nicotinamide phosphoribosyltransferase (Nampt) enzyme, the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD) salvage pathway, resulting in reduced levels of NAD.[5] miR-34a suppression of NAMPT gene expression also reduces levels of sirtuin 1.[5] Aging and obesity increase levels of miR-34a.[5] The pro-inflammatory transcription factor NF-κB (increasingly expressed with obesity and aging)[6] increases miR-34a expression by binding to its promoter region.[7] Inhibition of miR-34a in diet-induced obese mice restored levels of NAMPT and NAD, reducing inflammation and improving glucose tolerance.[8]

miR-34a represses the translation of sirtuin 1 (SIRT1) in liver by binding to the 3′-UTR region of SIRT1 messenger RNA, contributing to metabolic syndrome.[9][10] Downregulation of SIRT1 by miR-34a promotes cellular senescence and inflammation in vascular smooth muscle cells of old mice, similar to reduced SIRT1 in vascular smooth muscle cells in humans.[11] Impaired endothelial-dependent vasorelaxation caused by miR-34a can be ameliorated by SIRT1 overexpression.[11]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000284357 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Entrez Gene: MicroRNA 34a".
  4. ^ a b c Zeng H, Hu M, Lu Y, Zhang Z, Xu Y, Wang S, et al. (July 2019). "MicroRNA 34a promotes ionizing radiation-induced DNA damage repair in murine hematopoietic stem cells". FASEB Journal. 33 (7): 8138–8147. doi:10.1096/fj.201802639R. PMID 30922079.
  5. ^ a b c Yaku K, Okabe K, Nakagawa T (2018). "NAD Metabolism: Implications in Aging and Longevity". Ageing Research Reviews. 47: 1–17. doi:10.1016/j.arr.2018.05.006. PMID 29883761. S2CID 47002665.
  6. ^ Kauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A (2013). "Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders". Cellular Signalling. 25 (10): 1939–1948. doi:10.1016/j.cellsig.2013.06.007. PMID 23770291.
  7. ^ de Gregorio E, Colell A, Morales A, Marí M (2020). "Relevance of SIRT1-NF-κB Axis as Therapeutic Target to Ameliorate Inflammation in Liver Disease". International Journal of Molecular Sciences. 21 (11): 3858. doi:10.3390/ijms21113858. PMC 7312021. PMID 32485811.
  8. ^ Garten A, Schuster S, Penke M, Kiess W (2015). "Physiological and pathophysiological roles of NAMPT and NAD metabolism". Nature Reviews Endocrinology. 11 (9): 535–546. doi:10.1038/nrendo.2015.117. PMID 26215259. S2CID 11670137.
  9. ^ Cantó C, Auwerx J (2012). "Targeting sirtuin 1 to improve metabolism: all you need is NAD(+)?". Pharmacological Reviews. 64 (1): 166–187. doi:10.1124/pr.110.003905. PMC 3616312. PMID 22106091.
  10. ^ Imai S, Yoshino J (2013). "The importance of NAMPT/NAD/SIRT1 in the systemic regulation of metabolism and ageing". Diabetes, Obesity and Metabolism. 15 (Suppl 3): 26–33. doi:10.1111/dom.12171. PMC 3819727. PMID 24003918.
  11. ^ a b D'Onofrio N, Servillo L, Balestrieri ML (2018). "SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection". Antioxidants & Redox Signaling. 28 (8): 711–732. doi:10.1089/ars.2017.7178. PMC 5824538. PMID 28661724.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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