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

Frontiers in Cell and Developmental Biology

卷:9

Jorge Ruiz-Orera¹  M. Mar Albಠ Alba Escriche³  Camilla Bertani³  María Abad³  Elena Senís³  Marta Giménez-Alejandre³  Mireia Jiménez³  Albert Giralt⁴  Daniel del Toro⁴  Verónica Jiménez-Sábado⁶  Leif Hove-Madsen⁶  Héctor Peinado⁷  Marta Hergueta-Redondo⁷  Paolo Nuciforo⁸  Miriam Esgleas⁹  Sonia Najas⁹  Magdalena Götz⁹ 

[1] Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany;

[2] Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain;

[3] Cellular Plasticity and Cancer Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain;

[4] Department of Biological Sciences, Institute of Neurosciences, IDIBAPS, CIBERNED, University of Barcelona, Barcelona, Spain;

[5] Evolutionary Genomics Group, Research Programme on Biomedical Informatics, Hospital del Mar Medical Research Institute (IMIM) and Universitat Pompeu Fabra (UPF), Barcelona, Spain;

[6] Instituto de Investigación Biomédica Barcelona (IIBB-CSIC), Instituto de Investigación Biomédica Sant Pau (IIB-Sant Pau) and CIBERCV, Barcelona, Spain;

[7] Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain;

[8] Molecular Oncology Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain;

[9] Physiological Genomics, Biomedical Center (BMC), Helmholtz Center Munich, Institute of Stem Cell Research, Großhaderner Str, SyNergy Excellence Cluster, Ludwig-Maximilians-Universitaet (LMU), Munich, Germany;

关键词: microproteins;    micropeptides;    sORF encoded peptides;    TUNAR;    neural differentiation;    neurite formation;   

DOI  :  10.3389/fcell.2021.747667

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown