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Senís, E.* ; Esgleas Izquierdo, M. ; Najas, S. ; Jiménez-Sábado, V.* ; Bertani, C.* ; Giménez-Alejandre, M.* ; Escriche, A.* ; Ruiz-Orera, J.* ; Hergueta-Redondo, M.* ; Jimenez, M.* ; Giralt, A.* ; Nuciforo, P.* ; Albà, M.M.* ; Peinado, H.* ; Del Toro, D.* ; Hove-Madsen, L.* ; Götz, M. ; Abad, M.*

TUNAR lncRNA encodes a microprotein that regulates neural differentiation and neurite formation by modulating calcium dynamics.

Front. Cell Dev. Biol. 9:747667 (2021)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Tunar ; Calcium ; Long Non-coding Rnas ; Micropeptides ; Microproteins ; Neural Differentiation ; Neurite Formation ; Sorf Encoded Peptides; Prediction

ISSN (print) / ISBN 2296-634X

e-ISSN 2296-634X

Journal Frontiers in cell and developmental biology

Quellenangaben Volume: 9, Article Number: 747667

Publisher Frontiers

Publishing Place Lausanne

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Stem Cell Research (ISF)

Grants FEDER
Fero Foundation
La Caixa Foundation
Asociacion Espanola Contra el Cancer (AECC)
Cellex Foundation
Mutua Madrilena Foundation
Spanish Ministry of Science and Innovation
AECC Postdoctoral Fellowship
advanced ERC grant NeuroCentro and the German Research Foundation
Ramon y Cajal program
VHIO