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TUNAR lncRNA Encodes a Microprotein that Regulates Neural Differentiation and Neurite Formation by Modulating Calcium Dynamics

Authors :
Fundación Fero
Fundación la Caixa
Asociación Española Contra el Cáncer
Fundació Privada Cellex
Fundación Mutua Madrileña
Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
European Research Council
German Research Foundation
European Commission
Senís, Elena
Esgleas, Miriam
Najas, Sònia
Jiménez-Sábado, Verónica
Bertani, Camilla
Giménez-Alejandre, Marta
Escriche, Alba
Ruiz-Orera, Jorge
Hergueta-Redondo, Marta
Jiménez, Mireia
Giralt, Albert
Nuciforo, Paolo
Albà, M. Mar
Peinado, Héctor
Toro, Daniel del
Hove-Madsen, Leif
Götz, Magdalena
Abad, María
Fundación Fero
Fundación la Caixa
Asociación Española Contra el Cáncer
Fundació Privada Cellex
Fundación Mutua Madrileña
Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
European Research Council
German Research Foundation
European Commission
Senís, Elena
Esgleas, Miriam
Najas, Sònia
Jiménez-Sábado, Verónica
Bertani, Camilla
Giménez-Alejandre, Marta
Escriche, Alba
Ruiz-Orera, Jorge
Hergueta-Redondo, Marta
Jiménez, Mireia
Giralt, Albert
Nuciforo, Paolo
Albà, M. Mar
Peinado, Héctor
Toro, Daniel del
Hove-Madsen, Leif
Götz, Magdalena
Abad, María
Publication Year :
2021

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.

Details

Database :
OAIster
Publication Type :
Electronic Resource
Accession number :
edsoai.on1306017477
Document Type :
Electronic Resource