Heterogeneous nuclear ribonucleoprotein E3 modestly activates splicing of tau exon 10 via its proximal downstream intron, a hotspot for frontotemporal dementia mutations.

Gene
Yan WangAthena Andreadis

Abstract

The microtubule-associated protein tau is important to normal neuronal activity in the mammalian nervous system. Aggregated tau is the major component of neurofibrillary tangles (NFTs), structures present in the brains of people affected by neurodegenerative diseases called tauopathies. Tauopathies include Alzheimer's disease (AD), frontotemporal dementia with Parkinsonism (FTDP) and the early-onset dementia observed in Down syndrome (DS; trisomy 21). Splicing misregulation of adult-specific exon 10 results in expression of abnormal ratios of tau isoforms, leading to FTDP. Positions +3 to +19 of the intron downstream of exon 10 define a hotspot: Point mutations in it result in tauopathies. All these mutations increase exon 10 inclusion except for mutation +19, which almost entirely excludes exon 10. To investigate the tau connection between DS and AD, we examined splicing factors located on chromosome 21 for their effect on tau exon 10. By co-transfections, co-immunoprecipitations and RNAi constructs, we discovered that one of them, hnRNPE3 (PCBP3), modestly activates splicing of exon 10 by interacting with its proximal downstream intron around position +19. These results, coupled with the developmental profile of hnRNPE3, sugg...Continue Reading

References

Dec 16, 1998·Trends in Biochemical Sciences·A Ostareck-LedererM W Hentze
Oct 20, 1999·Journal of Molecular Neuroscience : MN·S AronovI Ginzburg
Dec 2, 1999·Neuroscience Letters·P D MehtaH M Wisniewski
Apr 25, 2000·Journal of Molecular Biology·J H KimS K Jang
May 11, 2002·RNA·Aleksandr V Makeyev, Stephen A Liebhaber
Mar 5, 2003·Brain : a Journal of Neurology·Prudence M StanfordPeter R Schofield
Dec 24, 2004·Biochimica Et Biophysica Acta·Michel Goedert, Ross Jakes
Jan 20, 2005·Gene·Stefan StammHermona Soreq
Apr 13, 2006·IUBMB Life·Francesca ArgellatiRoberta Ricciarelli
Jul 13, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hack Sun ChoiHorace H Loh
Aug 31, 2007·Journal of Neurochemistry·Chris ConradBradley T Hyman
Oct 10, 2007·Molecular and Cellular Biology·Timothée RevilBenoit Chabot
Nov 21, 2007·The Journal of Biological Chemistry·Klemens J Hertel
Apr 22, 2008·The FEBS Journal·Roberto ValverdeLynne Regan
May 30, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Fei LiuCheng-Xin Gong
Jul 12, 2008·Molecular Neurodegeneration·Fei Liu, Cheng-Xin Gong
Nov 11, 2008·Biochimica Et Biophysica Acta·Jamal TaziStefan Stamm
Dec 9, 2008·The Biochemical Journal·Jennifer C Long, Javier F Caceres
Aug 27, 2009·Journal of Neural Transmission·Kurt A Jellinger

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Citations

Sep 2, 2011·Journal of Molecular Neuroscience : MN·Payal RayJane Y Wu
Mar 15, 2014·Neuroscience Bulletin·Wei Qian, Fei Liu
May 24, 2011·Journal of Cellular Physiology·Athena Andreadis
Jan 15, 2014·Biochemical Pharmacology·Khalid IqbalCheng-Xin Gong
Aug 14, 2013·Molecular & Cellular Proteomics : MCP·Karen M ChapmanF Kent Hamra
Feb 28, 2014·Molecular Medicine Reports·Yin-Yin XiaYing-Xiong Wang
May 26, 2016·BMB Reports·Sun Ah ParkJean-Marc Gallo
Jun 23, 2020·Autoimmune Diseases·Ashraya JagadeeshRichard M Millis

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