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Pàgina inicial > Articles > Articles publicats > TUNAR lncRNA Encodes a Microprotein that Regulates Neural Differentiation and Neurite Formation by Modulating Calcium Dynamics |
Data: | 2021 |
Resum: | 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. |
Ajuts: | "la Caixa" Foundation HR18-00256 Ministerio de Ciencia e Innovación SAF2015-69413-R Ministerio de Ciencia e Innovación RTI2018-102046-B-I00 Ministerio de Ciencia e Innovación RYC-2013-14747 Ministerio de Ciencia e Innovación SAF2017-88019-C3-1R Ministerio de Ciencia e Innovación PID2020-116927RB-C21 Ministerio de Ciencia e Innovación PGC2018-094091-B-I00 Ministerio de Ciencia y Educación RTI2018-095580-A-I00 Agencia Estatal de Investigación RYC-2017-23486 |
Nota: | Altres ajuts: Asociación Española Contra el Cancer (AECC), Cellex Foundation, Mutua Madrileña Foundation. |
Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | Licroproteins ; Licropeptides ; Sorf encoded peptides ; TUNAR ; Neural differentiation ; Neurite formation ; Calcium ; Long non-coding RNAs |
Publicat a: | Frontiers in Cell and Developmental Biology, Vol. 9 (31 2021) , p. 747667, ISSN 2296-634X |
14 p, 3.8 MB |