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Acta Neuropathologica

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Open Access 12.08.2016 | Original Paper

Co-regulation of mRNA translation by TDP-43 and Fragile X Syndrome protein FMRP

verfasst von: Pritha Majumder, Jen-Fei Chu, Biswanath Chatterjee, Krishna B. S. Swamy, Che-Kun James Shen

Erschienen in: Acta Neuropathologica | Ausgabe 5/2016

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Abstract

For proper mammalian brain development and functioning, the translation of many neuronal mRNAs needs to be repressed without neuronal activity stimulations. We have discovered that the expression of a subclass of neuronal proteins essential for neurodevelopment and neuron plasticity is co-regulated at the translational level by TDP-43 and the Fragile X Syndrome protein FMRP. Using molecular, cellular and imaging approaches, we show that these two RNA-binding proteins (RBP) co-repress the translation initiation of Rac1, Map1b and GluR1 mRNAs, and consequently the hippocampal spinogenesis. The co-repression occurs through binding of TDP-43 to mRNA(s) at specific UG/GU sequences and recruitment of the inhibitory CYFIP1-FMRP complex by its glycine-rich domain. This novel regulatory scenario could be utilized to silence a significant portion of around 160 common target mRNAs of the two RBPs. The study establishes a functional/physical partnership between FMRP and TDP-43 that mechanistically links several neurodevelopmental disorders and neurodegenerative diseases.

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Titel: Co-regulation of mRNA translation by TDP-43 and Fragile X Syndrome protein FMRP
verfasst von: Pritha Majumder
Jen-Fei Chu
Biswanath Chatterjee
Krishna B. S. Swamy
Che-Kun James Shen
Publikationsdatum: 12.08.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Acta Neuropathologica / Ausgabe 5/2016
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-016-1603-8

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Co-regulation of mRNA translation by TDP-43 and Fragile X Syndrome protein FMRP

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