Web of Science: 16 citations, Scopus: 16 citations, Google Scholar: citations,
TUNAR lncRNA Encodes a Microprotein that Regulates Neural Differentiation and Neurite Formation by Modulating Calcium Dynamics
Senís, Elena (Vall d'Hebron Institut d'Oncologia)
Esgleas, Miriam (Ludwig-Maximilians-Universitaet)
Najas, Sonia (Ludwig-Maximilians-Universitaet)
Jiménez-Sábado, Verónica (Institut d'Investigació Biomèdica Sant Pau)
Bertani, Camilla (Vall d'Hebron Institut d'Oncologia)
Giménez-Alejandre, Marta (Vall d'Hebron Institut d'Oncologia)
Escriche, Alba (Vall d'Hebron Institut d'Oncologia)
Ruiz-Orera, Jorge (Max Delbrück Center for Molecular Medicine in the Helmholtz Association. MDC)
Hergueta-Redondo, Marta (Centro Nacional de Investigaciones Oncológicas)
Jiménez, Mireia (Vall d'Hebron Institut d'Oncologia)
Giralt, Albert (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Nuciforo, Paolo (Vall d'Hebron Institut d'Oncologia)
Albà, M. Mar (Institució Catalana de Recerca i Estudis Avançats)
Peinado, Héctor (Centro Nacional de Investigaciones Oncológicas)
Toro, Daniel del (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Hove-Madsen, Leif (Institut d'Investigació Biomèdica Sant Pau)
Götz, Magdalena (Ludwig-Maximilians-Universitaet)
Abad, María (Vall d'Hebron Institut d'Oncologia)
Universitat Autònoma de Barcelona

Date: 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.
Grants: "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
Note: Altres ajuts: Asociación Española Contra el Cancer (AECC), Cellex Foundation, Mutua Madrileña Foundation.
Rights: 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. Creative Commons
Language: Anglès
Document: Article ; recerca ; Versió publicada
Subject: Licroproteins ; Licropeptides ; Sorf encoded peptides ; TUNAR ; Neural differentiation ; Neurite formation ; Calcium ; Long non-coding RNAs
Published in: Frontiers in Cell and Developmental Biology, Vol. 9 (31 2021) , p. 747667, ISSN 2296-634X

DOI: 10.3389/fcell.2021.747667
PMID: 35036403


14 p, 3.8 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles

 Record created 2022-07-26, last modified 2024-05-29



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