کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6262303 | 1613795 | 2016 | 7 صفحه PDF | دانلود رایگان |

- TBPH is the fly ortholog of human TDP-43.
- Drosophila models of TDP-43 proteinopathy mirror phenotypic features of ALS.
- TBPH-null flies show a decreased expression of Futsch protein but not mRNA.
- TBPH binds an UG-rich sequence localized within the 5â²UTR of futsch mRNA.
- TBPH binding to the 5â²UTR modulates positively its expression at the translational level.
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 5â²UTR of futsch mRNA and translation is positively modulated by this binding. Most importantly, this function is also conserved in human TDP-43. This result can therefore represent the first step in elucidating the relationship between TDP-43, protein translation, and eventual disease onset or progression.This article is part of a Special Issue entitled SI:RNA Metabolism in Disease.
187This article is part of a Special Issue entitled SI:RNA Metabolism in Disease.
Journal: Brain Research - Volume 1647, 15 September 2016, Pages 50-56