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Title: | TUNAR lncRNA Encodes a Microprotein that Regulates Neural Differentiation and Neurite Formation by Modulating Calcium Dynamics |
Author: | Senís, Elena Esgleas, Miriam Najas, Sonia Jiménez-Sábado, Veronica Bertani, Camilla Giménez Alejandre, Marta. Escriche, Alba Ruiz Orera, Jorge Hergueta Redondo, Marta Jiménez, Mireia Giralt Torroella, Albert Nuciforo, Paolo Albà, M. Mar Peinado, Hector Toro, Daniel del Hove-Madsen, Leif Götz, Magdalena Abad, María Lluisa |
Keywords: | Neurobiologia del desenvolupament Calci Neuroplasticitat Developmental neurobiology Calcium Neuroplasticity |
Issue Date: | 31-Dec-2021 |
Publisher: | Frontiers Media |
Abstract: | Long noncoding RNAs (lncRNAs) are regulatory molecules which have been traditionally considered as 'non-coding'. Strikingly, recent evidence has demonstrated that many non-coding regions, including lncRNAs, do in fact contain small-open reading frames that code for small proteins that have been called microproteins. Only a few of them have been characterized so far, but they display key functions in a wide variety of cellular processes. Here, we show that TUNAR lncRNA encodes an evolutionarily conserved microprotein expressed in the nervous system that we have named pTUNAR. pTUNAR deficiency in mouse embryonic stem cells improves their differentiation potential towards neural lineage both in vitro and in vivo. Conversely, pTUNAR overexpression impairs neuronal differentiation by reduced neurite formation in different model systems. At the subcellular level, pTUNAR is a transmembrane protein that localizes in the endoplasmic reticulum and interacts with the calcium transporter SERCA2. pTUNAR overexpression reduces cytoplasmatic calcium, consistent with a possible role of pTUNAR as an activator of SERCA2. Altogether, our results suggest that our newly discovered microprotein has an important role in neural differentiation and neurite formation through the regulation of intracellular calcium. From a more general point of view, our results provide a proof of concept of the role of lncRNAs-encoded microproteins in neural differentiation. |
Note: | Reproducció del document publicat a: https://doi.org/10.3389/fcell.2021.747667 |
It is part of: | Frontiers In Cell And Developmental Biology, 2021, vol. 9, p. 747667 |
URI: | http://hdl.handle.net/2445/183231 |
Related resource: | https://doi.org/10.3389/fcell.2021.747667 |
ISSN: | 2296-634X |
Appears in Collections: | Articles publicats en revistes (Biomedicina) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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