Regulation of a TrkB Alternative Transcript by MicroRNAs

Overview

Journal Dement Geriatr Cogn Dis Extra

Publisher Karger

Specialty Geriatrics

Date 2014 Oct 23

PMID 25337079

Citations 1

Authors

Jenny Wong

Affiliations

Soon will be listed here.

Abstract

Background/aims: Tropomyosin-related kinase B receptor (TrkB)-mediated signaling is vital for neuronal differentiation, survival, plasticity, and cognition. In this study, the focus was placed on TrkB-Shc, a neuron-specific transcript, to determine if microRNAs (miRNAs) play a role in TrkB-Shc regulation.

Methods: A combination of bioinformatics and molecular gene expression analysis techniques was used to assess the effect of miR-409-3p and miR-216b on TrkB-Shc expression.

Results: miR-409-3p and miR-216b were found to regulate the TrkB-Shc 3'UTR through the identified putative binding sites. When the effect of the miRNAs on TrkB was assessed using SHSY5Y neuronal cells, differential effects were observed between mRNA and protein expression.

Conclusion: This study highlights the importance of miRNA-mediated regulation in TrkB signaling.

Citing Articles

A Review of Molecular Interplay between Neurotrophins and miRNAs in Neuropsychological Disorders.

Abdolahi S, Zare-Chahoki A, Noorbakhsh F, Gorji A Mol Neurobiol. 2022; 59(10):6260-6280.

PMID: 35916975 PMC: 9463196. DOI: 10.1007/s12035-022-02966-5.

References

Allen S, Wilcock G, Dawbarn D . Profound and selective loss of catalytic TrkB immunoreactivity in Alzheimer's disease. Biochem Biophys Res Commun. 1999; 264(3):648-51. DOI: 10.1006/bbrc.1999.1561. View

Barbacid M . The Trk family of neurotrophin receptors. J Neurobiol. 1994; 25(11):1386-403. DOI: 10.1002/neu.480251107. View

To K, Zhan Z, Litman T, Bates S . Regulation of ABCG2 expression at the 3' untranslated region of its mRNA through modulation of transcript stability and protein translation by a putative microRNA in the S1 colon cancer cell line. Mol Cell Biol. 2008; 28(17):5147-61. PMC: 2519722. DOI: 10.1128/MCB.00331-08. View

Wong J, Garner B . Evidence that truncated TrkB isoform, TrkB-Shc can regulate phosphorylated TrkB protein levels. Biochem Biophys Res Commun. 2012; 420(2):331-5. DOI: 10.1016/j.bbrc.2012.02.159. View

Valencia-Sanchez M, Liu J, Hannon G, Parker R . Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 2006; 20(5):515-24. DOI: 10.1101/gad.1399806. View

Maussion G, Yang J, Yerko V, Barker P, Mechawar N, Ernst C . Regulation of a truncated form of tropomyosin-related kinase B (TrkB) by Hsa-miR-185* in frontal cortex of suicide completers. PLoS One. 2012; 7(6):e39301. PMC: 3382618. DOI: 10.1371/journal.pone.0039301. View

Wong J, Garner B, Halliday G, Kwok J . Srp20 regulates TrkB pre-mRNA splicing to generate TrkB-Shc transcripts with implications for Alzheimer's disease. J Neurochem. 2012; 123(1):159-71. DOI: 10.1111/j.1471-4159.2012.07873.x. View

Felekkis K, Touvana E, Stefanou C, Deltas C . microRNAs: a newly described class of encoded molecules that play a role in health and disease. Hippokratia. 2011; 14(4):236-40. PMC: 3031315. View

Stoilov P, Castren E, Stamm S . Analysis of the human TrkB gene genomic organization reveals novel TrkB isoforms, unusual gene length, and splicing mechanism. Biochem Biophys Res Commun. 2002; 290(3):1054-65. DOI: 10.1006/bbrc.2001.6301. View

10.

Beveridge N, Tooney P, Carroll A, Tran N, Cairns M . Down-regulation of miR-17 family expression in response to retinoic acid induced neuronal differentiation. Cell Signal. 2009; 21(12):1837-45. DOI: 10.1016/j.cellsig.2009.07.019. View

11.

Smirnova L, Grafe A, Seiler A, Schumacher S, Nitsch R, Wulczyn F . Regulation of miRNA expression during neural cell specification. Eur J Neurosci. 2005; 21(6):1469-77. DOI: 10.1111/j.1460-9568.2005.03978.x. View

12.

Shankar G, Walsh D . Alzheimer's disease: synaptic dysfunction and Abeta. Mol Neurodegener. 2009; 4:48. PMC: 2788538. DOI: 10.1186/1750-1326-4-48. View

13.

Ohira K, Hayashi M . Expression of TrkB subtypes in the adult monkey cerebellar cortex. J Chem Neuroanat. 2003; 25(3):175-83. DOI: 10.1016/s0891-0618(02)00096-0. View

14.

Wong J, Duncan C, Beveridge N, Webster M, Cairns M, Weickert C . Expression of NPAS3 in the human cortex and evidence of its posttranscriptional regulation by miR-17 during development, with implications for schizophrenia. Schizophr Bull. 2012; 39(2):396-406. PMC: 3576160. DOI: 10.1093/schbul/sbr177. View

15.

Guidi M, Muinos-Gimeno M, Kagerbauer B, Marti E, Estivill X, Espinosa-Parrilla Y . Overexpression of miR-128 specifically inhibits the truncated isoform of NTRK3 and upregulates BCL2 in SH-SY5Y neuroblastoma cells. BMC Mol Biol. 2010; 11:95. PMC: 3019150. DOI: 10.1186/1471-2199-11-95. View

16.

Lal A, Navarro F, Maher C, Maliszewski L, Yan N, ODay E . miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elements. Mol Cell. 2009; 35(5):610-25. PMC: 2757794. DOI: 10.1016/j.molcel.2009.08.020. View

17.

Hoozemans J, Chafekar S, Baas F, Eikelenboom P, Scheper W . Always around, never the same: pathways of amyloid beta induced neurodegeneration throughout the pathogenic cascade of Alzheimer's disease. Curr Med Chem. 2006; 13(22):2599-605. DOI: 10.2174/092986706778201585. View

18.

Miska E, Alvarez-Saavedra E, Townsend M, Yoshii A, Sestan N, Rakic P . Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol. 2004; 5(9):R68. PMC: 522875. DOI: 10.1186/gb-2004-5-9-r68. View

19.

Minichiello L, Korte M, Wolfer D, Kuhn R, Unsicker K, Cestari V . Essential role for TrkB receptors in hippocampus-mediated learning. Neuron. 1999; 24(2):401-14. DOI: 10.1016/s0896-6273(00)80853-3. View

20.

Kosik K . The neuronal microRNA system. Nat Rev Neurosci. 2006; 7(12):911-20. DOI: 10.1038/nrn2037. View