TBPH/TDP-43 modulates translation of Drosophila futsch mRNA through an UG-rich sequence within its 5'UTR

Brain Research
Maurizio RomanoEmanuele Buratti

Abstract

Nuclear factor TDP-43 is an evolutionarily conserved multifunctional RNA-binding protein associated with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). In recent years, Drosophila models of ALS based on TDP-43 knockdown/overexpression have allowed to find several connections with disease. Among these, we have previously described that silencing the expression of its fly ortholog (TBPH) can alter the expression of the neuronal microtubule-associated protein Futsch leading to alterations of neuromuscular junction (NMJ) organization. In particular, TBPH knocked out flies displayed a significant reduction of Futsch protein levels, although minimal variation in the futsch mRNA content was observed. These conclusions were recently validated in an independent study. Together, these observations strongly support the hypothesis that TBPH might regulate the translation of futsch mRNA. However, the mechanism of TBPH interference in futsch mRNA translation is still unknown. In this work, we use EMSA experiments coupled with RNA-protein co-immunprecipitations and luciferase assays to show that TBPH interacts with a stretch of UG within the 5'UTR of futsch mRNA and translation is positively modulated by thi...Continue Reading

References

Apr 14, 2005·Journal of Molecular Biology·Youhna M AyalaFrancisco E Baralle
May 12, 2009·Nucleic Acids Research·Andrea D'AmbrogioFrancisco E Baralle
Nov 6, 2010·The Journal of Biological Chemistry·Chantelle F SephtonGang Yu
Dec 3, 2010·Neuro-degenerative Diseases·Iga Wegorzewska, Robert H Baloh
Dec 7, 2010·The EMBO Journal·Youhna M AyalaFrancisco E Baralle
Mar 2, 2011·Nature Neuroscience·James R TollerveyJernej Ule
Mar 2, 2011·Nature Neuroscience·Magdalini PolymenidouDon W Cleveland
Dec 1, 2011·Nature Reviews. Neuroscience·Edward B LeeJohn Q Trojanowski
Apr 27, 2012·Trends in Biochemical Sciences·Emanuele Buratti, Francisco E Baralle
May 12, 2012·Journal of Amino Acids·Maurizio RomanoEmanuele Buratti
Jun 14, 2012·Comparative and Functional Genomics·Patricia R AraujoLuiz O F Penalva
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Jan 3, 2013·Molecular and Cellular Neurosciences·Veronique V BelzilLeonard Petrucelli
Aug 1, 2013·Human Molecular Genetics·Jonathan Janssens, Christine Van Broeckhoven
Oct 12, 2013·International Journal of Molecular Sciences·Yu-Chih LiuKuen-Jer Tsai
Aug 5, 2014·Neurobiology of Disease·Giulia RomanoFabian Feiguin
Nov 28, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alyssa N CoyneDaniela C Zarnescu

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Citations

Mar 27, 2016·Journal of Neurochemistry·Antonia Ratti, Emanuele Buratti
Feb 9, 2018·Journal of Neural Transmission·S BräuerA Hermann
Nov 17, 2017·Scientific Reports·Josiah J HerzogSuzanne Paradis
May 18, 2020·Journal of Molecular Neuroscience : MN·E Srinivasan, R Rajasekaran
Sep 2, 2017·Frontiers in Cellular Neuroscience·Alyssa N CoyneDaniela C Zarnescu
Apr 8, 2017·Frontiers in Molecular Neuroscience·Gianluca CestraMauro Cozzolino
May 4, 2017·Molecular Neurobiology·Moritz OberstadtMax Holzer
Jul 25, 2019·Acta Neuropathologica·Aneesh DondePhilip C Wong
Jan 23, 2021·International Journal of Molecular Sciences·Sophie LayalleLaurent Soustelle
May 2, 2018·Brain Research·Diana FerroDaniela C Zarnescu
Aug 6, 2021·Frontiers in Cellular Neuroscience·Benjamin L Zaepfel, Jeffrey D Rothstein

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