Journal
HUMAN MOLECULAR GENETICS
Volume 26, Issue 14, Pages 2732-2746Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddx160
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Funding
- Associazione Italiana Ricerca sul Cancro [AIRC IG17278]
- Worldwide Cancer Research [AICR-UK 14-0333]
- University of Rome Foro Italico [RIC052016]
- Telethon [GGP14095]
- Ministry of Health Ricerca Corrente
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Brain development involves proliferation, migration and specification of neural progenitor cells, culminating in neuronal circuit formation. Mounting evidence indicates that improper regulation of RNA binding proteins (RBPs), including members of the FET (FUS, EWS, TAF15) family, results in defective cortical development and/or neurodegenerative disorders. However, in spite of their physiological relevance, the precise pattern of FET protein expression in developing neurons is largely unknown. Herein, we found that FUS, EWS and TAF15 expression is differentially regulated during brain development, both in time and in space. In particular, our study identifies a fine-tuned regulation of FUS and EWS during neuronal differentiation, whereas TAF15 appears to be more constitutively expressed. Mechanistically FUS and EWS protein expression is regulated at the post-transcriptional level during neuron differentiation and brain development. Moreover, we identified miR-141 as a key regulator of these FET proteins that modulate their expression levels in differentiating neuronal cells. Thus, our studies uncover a novel link between post-transcriptional regulation of FET proteins expression and neurogenesis.
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