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Hibernation is a complex physiological response that some mammalian species employ to evade energetic demands. Previous work in mammalian hibernators suggests that hibernation is activated not by a set of genes unique to hibernators, but by differential expression of genes that are present in all mammals. This question of universal genetic mechanisms requires further investigation and can only be tested through additional investigations of phylogenetically dispersed species. To explore this question, we use RNA-Seq to investigate gene expression dynamics as they relate to the varying physiological states experienced throughout the year in a group of primate hibernators—Madagascar's dwarf lemurs (genus Cheirogaleus). In a novel experimental approach, we use longitudinal sampling of biological tissues as a method for capturing gene expression profiles from the same individuals throughout their annual hibernation cycle. We identify 90 candidate genes that have variable expression patterns when comparing two active states (Active 1 and Active 2) with a torpor state. These include genes that are involved in metabolic pathways, feeding behavior, and circadian rhythms, as might be expected to correlate with seasonal physiological state changes. The identified genes appear to be critical for maintaining the health of an animal that undergoes prolonged periods of metabolic depression concurrent with the hibernation phenotype. By focusing on these differentially expressed genes in dwarf lemurs, we compare gene expression patterns in previously studied mammalian hibernators. Additionally, by employing evolutionary rate analysis, we find that hibernation-related genes do not evolve under positive selection in hibernating species relative to nonhibernators. ; This work was supported by grants from the Society of Integrative and Comparative Biology and Sigma Xi to S.L.F., a National Science Foundation Doctoral Research Improvement Grant (NSF-BCS 1455809 to A.D.Y. and S.L.F.), a grant from the Duke University Institute for Genome Science and Policy to A.D.Y., and funding from the Ministerio de Economía y Competitividad of the Spanish Government (BIO2009-08160 to J.L.V.C. and BFU2012-36820 to J.L.V.C. and M.M.A.); and Fundació ICREA to M.M.A. ; Peer reviewed

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. ; Most people in theworld (∼90%) are infected by the Epstein-Barr virus (EBV), which establishes itself permanently in B cells. Infection by EBV is related to a number of diseases including infectious mononucleosis, multiple sclerosis, and different types of cancer. So far, only seven complete EBV strains have been described, all of themcoming from donors presenting EBV-related diseases. To perform a detailed comparative genomic analysis of EBV including, for the first time, EBV strains derived from healthy individuals, we reconstructed EBV sequences infecting lymphoblastoid cell lines (LCLs) from the 1000 Genomes Project. As strain B95-8 was used to transform B cells to obtain LCLs, it is always present, but a specific deletion in its genome sets it apart from natural EBV strains. After studying hundreds of individuals, we determined the presence of natural EBV in at least 10 of them and obtained a set of variants specific to wild-type EBV. By mapping the natural EBV reads into the EBV reference genome (NC007605), we constructed nearly complete wild-type viralgenomesfrom three individuals.Adding themtothefivedisease-derived EBVgenomicsequences available in the literature, we performed an in-depth comparative genomic analysis. We found that latency genes harbor more nucleotide diversity than lytic genes and that six out of nine latency-related genes, as well as other genes involved in viral attachment and entry into host cells, packaging, and the capsid, present the molecular signature of accelerated protein evolution rates, suggesting rapid host-parasite coevolution. © 2014 The Author(s). ; This work was supported by the Spanish Multiple Sclerosis Network (REEM), of the Instituto de Salud Carlos III (RD07/0060 and RD12/0032/0011) to A.N., A.A., and P.V.; by the Spanish Government Grants BFU2009-13409-C02-02 and BFU2012-38236 to A.N.; and by FEDER. ; Peer Reviewed

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. ; Work in the Abad lab is supported by VHIO, Fero Foundation, La Caixa Foundation (HR18-00256), Asociación Española Contra el Cancer (AECC), Cellex Foundation, Mutua Madrileña Foundation and by grants from the Spanish Ministry of Science and Innovation (SAF2015-69413-R; RTI2018-102046-B-I00). M.A. was recipient of a Ramon y Cajal contract from the Spanish Ministry of Science and Innovation (RYC-2013-14747). E.S. was recipient of a AECC Postdoctoral Fellowship. L.H-M. also acknowledges funding from grants SAF2017-88019-C3-1R y PID2020-116927RB-C21 from the Spanish Government. MG is supported by the advanced ERC grant NeuroCentro and the German Research Foundation (SFB870; SPP2202; SPP2306; SYNERGY; TRR274). DT is supported by the Ramón y Cajal program (RYC-2017-23486/RTI2018-095580-A-I00). MMA acknowledges funding from the Spanish Ministry of Science and Innovation PGC2018-094091-B-I00 co-funded by FEDER.