{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T08:40:03Z","timestamp":1778056803499,"version":"3.51.4"},"reference-count":62,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key R&amp;D Program of China","award":["National Key R&D Program of China"],"award-info":[{"award-number":["National Key R&D Program of China"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31961133026"],"award-info":[{"award-number":["31961133026"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Noncoding RNAs have been known to contribute to a variety of fundamental life processes, such as development, metabolism, and circadian rhythms. However, much remains unrevealed in the huge noncoding RNA datasets, which require further bioinformatic analysis and experimental investigation\u2014and in particular, the coding potential of lncRNAs and the functions of lncRNA-encoded peptides have not been comprehensively studied to date. Through integrating the time-course experimentation with state-of-the-art computational techniques, we studied tens of thousands of zebrafish lncRNAs from our own experiments and from a published study including time-series transcriptome analyses of the testis and the pineal gland. Rhythmicity analysis of these data revealed approximately 700 rhythmically expressed lncRNAs from the pineal gland and the testis, and their GO, COG, and KEGG pathway functions were analyzed. Comparative and conservative analyses determined 14 rhythmically expressed lncRNAs shared between both the pineal gland and the testis, and 15 pineal gland lncRNAs as well as 3 testis lncRNAs conserved among zebrafish, mice, and humans. Further, we computationally analyzed the conserved lncRNA-encoded peptides, and revealed three pineal gland and one testis lncRNA-encoded peptides conserved among these three species, which were further investigated for their three-dimensional (3D) structures and potential functions. Our computational findings provided novel annotations and regulatory mechanisms for hundreds of rhythmically expressed pineal gland and testis lncRNAs in zebrafish, and set the stage for their experimental studies in the near future.<\/jats:p>","DOI":"10.3390\/ijms22157810","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:07:40Z","timestamp":1626998860000},"page":"7810","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Identification of Rhythmically Expressed LncRNAs in the Zebrafish Pineal Gland and Testis"],"prefix":"10.3390","volume":"22","author":[{"given":"Shital Kumar","family":"Mishra","sequence":"first","affiliation":[{"name":"Center for Circadian Clocks, Soochow University, Suzhou 215123, China"},{"name":"School of Biology & Basic Medical Sciences, Medical College, Soochow University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taole","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Circadian Clocks, Soochow University, Suzhou 215123, China"},{"name":"School of Biology & Basic Medical Sciences, Medical College, Soochow University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2420-3147","authenticated-orcid":false,"given":"Han","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Circadian Clocks, Soochow University, Suzhou 215123, China"},{"name":"School of Biology & Basic Medical Sciences, Medical College, Soochow University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"The FANTOM Consortium, Carninci, P., Kasukawa, T., Katayama, S., Gough, J., Frith, M.C., Maeda, N., Oyama, R., Ravasi, T., and Lenhard, B. (2005). The Transcriptional Landscape of the Mammalian Genome. Science, 309, 1559\u20131563.","DOI":"10.1126\/science.1112014"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.cell.2010.09.001","article-title":"Long Noncoding RNAs with Enhancer-like Function in Human Cells","volume":"143","author":"Derrien","year":"2010","journal-title":"Cell"},{"key":"ref_3","first-page":"223","article-title":"Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals","volume":"458","author":"Guttman","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"32753","DOI":"10.1038\/srep32753","article-title":"HIPSTR and thousands of lncRNAs are heterogeneously expressed in human embryos, primordial germ cells and stable cell lines","volume":"6","author":"Yunusov","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1007\/s13105-012-0166-y","article-title":"Regulatory long non-coding RNA and its functions","volume":"68","author":"Huang","year":"2012","journal-title":"J. Physiol. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.febslet.2015.01.013","article-title":"Computational identification of epigenetically regulated lncRNAs and their associated genes based on integrating genomic data","volume":"589","author":"Zhao","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chen, J., Wang, Y., Wang, C., Hu, J.-F., and Li, W. (2020). LncRNA Functions as a New Emerging Epigenetic Factor in Determining the Fate of Stem Cells. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00277"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.cell.2015.01.009","article-title":"A Micropeptide Encoded by a Putative Long Noncoding RNA Regulates Muscle Performance","volume":"160","author":"Anderson","year":"2015","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1039\/C4MB00478G","article-title":"Identification of cancer-related lncRNAs through integrating genome, regulome and transcriptome features","volume":"11","author":"Zhao","year":"2014","journal-title":"Mol. BioSyst."},{"key":"ref_10","first-page":"3769","article-title":"A micropeptide encoded by lncRNA MIR155HG suppresses autoimmune inflammation via modulating antigen presentation","volume":"26","author":"Kluiver","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/s41419-019-1767-y","article-title":"A novel mitochondrial micropeptide MPM enhances mitochondrial respiratory activity and promotes myogenic differentiation","volume":"10","author":"Lin","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sousa, M.E., and Farkas, M.H. (2018). Micropeptide. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007764"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.jacc.2015.12.051","article-title":"Long Noncoding RNAs from Clinical Genetics to Therapeutic Targets?","volume":"67","author":"Boon","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wu, S., Zhu, X., Zhang, L., Deng, J., Li, F., Guo, B., Zhang, S., Wu, R., and Zhang, Z. (2020). LncRNA-encoded polypeptide ASRPS inhibits triple-negative breast cancer angiogenesis. J. Exp. Med., 217.","DOI":"10.1084\/jem.20190950"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1084\/jem.20192009","article-title":"When non-coding is not enough","volume":"217","author":"Anfossi","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1186\/s12935-020-01589-x","article-title":"Emerging role of long noncoding RNA-encoded micropeptides in cancer","volume":"20","author":"Ye","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.neo.2014.11.004","article-title":"A Long Noncoding RNA Perturbs the Circadian Rhythm of Hepatoma Cells to Facilitate Hepatocarcinogenesis","volume":"17","author":"Cui","year":"2015","journal-title":"Neoplasia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.1093\/nar\/gkx156","article-title":"A class of circadian long non-coding RNAs mark enhancers modulating long-range circadian gene regulation","volume":"45","author":"Fan","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13319","DOI":"10.1073\/pnas.1207748109","article-title":"Circadian changes in long noncoding RNAs in the pineal gland","volume":"109","author":"Coon","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/BF02617764","article-title":"Input and output signals in a model neural system: The regulation of melatonin production in the pineal gland","volume":"6","author":"Klein","year":"1970","journal-title":"In Vitro"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1177\/0748730415618297","article-title":"Timing in the Testis","volume":"31","author":"Bittman","year":"2015","journal-title":"J. Biol. Rhythm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1210\/me.2002-0184","article-title":"No Circadian Rhythms in Testis: Period1 Expression Is Clock Independent and Developmentally Regulated in the Mouse","volume":"17","author":"Morse","year":"2003","journal-title":"Mol. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1177\/0748730404274078","article-title":"The Thymus Is Similar to the Testis in Its Pattern of Circadian Clock Gene Expression","volume":"20","author":"Alvarez","year":"2005","journal-title":"J. Biol. Rhythm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.febslet.2011.04.007","article-title":"It\u2019s time to swim! Zebrafish and the circadian clock","volume":"585","author":"Vatine","year":"2011","journal-title":"FEBS Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ymeth.2014.01.001","article-title":"Studying circadian rhythms in Drosophila melanogaster","volume":"68","author":"Tataroglu","year":"2014","journal-title":"Methods"},{"key":"ref_26","first-page":"506","article-title":"Functional Development of the Circadian Clock in the Zebrafish Pineal Gland","volume":"2014","author":"Foulkes","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"149","DOI":"10.12717\/DR.2013.17.3.149","article-title":"Potency of Melatonin in Living Beings","volume":"17","author":"Choi","year":"2013","journal-title":"Dev. Reprod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14712","DOI":"10.1073\/pnas.0704588104","article-title":"Light signaling to the zebrafish circadian clock by Cryptochrome 1a","volume":"104","author":"Tamai","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1756-0381-3-2","article-title":"Large scale analysis of positional effects of single-base mismatches on microarray gene expression data","volume":"3","author":"Duan","year":"2010","journal-title":"BioData Min."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1101\/gad.17446611","article-title":"Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses","volume":"25","author":"Cabili","year":"2011","journal-title":"Genes Dev."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Tovin, A., Alon, S., Ben-Moshe, Z., Mracek, P., Vatine, G., Foulkes, N.S., Jacob-Hirsch, J., Rechavi, G., Toyama, R., and Coon, S.L. (2012). Systematic Identification of Rhythmic Genes Reveals camk1gb as a New Element in the Circadian Clockwork. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1003116"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Barik, S. (2019). Molecular Interactions between Pathogens and the Circadian Clock. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235824"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Thiriet, M. (2012). Control of Cell Fate in the Circulatory and Ventilatory Systems. Control of Cell Fate in the Circulatory and Ventilatory Systems, Springer Science & Business Media.","DOI":"10.1007\/978-1-4614-0329-6"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1146\/annurev-genet-102209-163432","article-title":"Circadian Control of Global Gene Expression Patterns","volume":"44","author":"Doherty","year":"2010","journal-title":"Annu. Rev. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/bioinformatics\/btr064","article-title":"FIMO: Scanning for occurrences of a given motif","volume":"27","author":"Grant","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1093\/bib\/bbx117","article-title":"Microbial genome analysis: The COG approach","volume":"20","author":"Galperin","year":"2019","journal-title":"Brief. Bioinform."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Fang, G., Bhardwaj, N., Robilotto, R., and Gerstein, M.B. (2010). Getting Started in Gene Orthology and Functional Analysis. PLoS Comput. Biol., 6.","DOI":"10.1371\/journal.pcbi.1000703"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"541786","DOI":"10.1100\/2012\/541786","article-title":"Molecular Mechanisms and Function Prediction of Long Noncoding RNA","volume":"2012","author":"Ma","year":"2012","journal-title":"Sci. World J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.omtn.2020.05.018","article-title":"Computational Methods and Applications for Identifying Disease-Associated lncRNAs as Potential Biomarkers and Therapeutic Targets","volume":"21","author":"Yan","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s41419-020-2570-5","article-title":"The micropeptide LEMP plays an evolutionarily conserved role in myogenesis","volume":"11","author":"Wang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nrg2934","article-title":"RNA sequencing: Advances, challenges and opportunities","volume":"12","author":"Ozsolak","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Yu, F., Zhang, Y., Cheng, C., Wang, W., Zhou, Z., Rang, W., Yu, H., Wei, Y., Wu, Q., and Zhang, Y. (2020). Poly(A)-seq: A method for direct sequencing and analysis of the transcriptomic poly(A)-tails. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0234696"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1080\/15548627.2016.1183843","article-title":"The circadian clock regulates autophagy directly through the nuclear hormone receptor Nr1d1\/Reverb\u03b1 and indirectly via Cebpb\/(C\/ebp\u03b2) in zebrafish","volume":"2","author":"Huang","year":"2016","journal-title":"Autophagy"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_45","first-page":"85","article-title":"Overview of Circadian Rhythms","volume":"25","author":"Vitaterna","year":"2001","journal-title":"Alcohol Res. Health"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Hu, X., Chen, W., Li, J., Huang, S., Xu, X., Zhang, X., Xiang, S., and Liu, C. (2018). ZFLNC: A comprehensive and well-annotated database for zebrafish lncRNA. Database, 2018.","DOI":"10.1093\/database\/bay114"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mishra, S.K., and Wang, H. (2021). Computational Analysis Predicts Hundreds of Coding lncRNAs in Zebrafis. Biology, 10.","DOI":"10.3390\/biology10050371"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1093\/nar\/gks1099","article-title":"CPAT: Coding-Potential As-sessment Tool using an alignment-free logistic regression model","volume":"41","author":"Chen","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3826","DOI":"10.1172\/JCI120874","article-title":"High-accuracy determination of internal circadian time from a single blood sample","volume":"128","author":"Wittenbrink","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1093\/bioinformatics\/btw405","article-title":"MetaCycle: An Integrated R Package to Evalu-ate Periodicity in Large Scale Data\u201d","volume":"32","author":"Wu","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zielinski, T., Moore, A.M., Troup, E., Halliday, K.J., and Millar, A.J. (2014). Strengths and Limitations of Period Estimation Methods for Circadian Data. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096462"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1093\/bioinformatics\/btn654","article-title":"bioDBnet: The biological database network","volume":"25","author":"Mudunuri","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_53","first-page":"D87","article-title":"JASPAR 2020: Update of the open-access database of transcription factor binding profiles","volume":"48","author":"Fornes","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/bib\/6.3.298","article-title":"Get ready to GO! A biologist\u2019s guide to the Gene Ontology","volume":"6","author":"Lomax","year":"2005","journal-title":"Brief. Bioinform."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene Ontology: Tool for the unification of biology","volume":"25","author":"Botstein","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.1093\/nar\/gkn176","article-title":"High-throughput functional annotation and data mining with the Blast2GO suite","volume":"36","author":"Terol","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID Bioinformatics Resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/nmeth.4346","article-title":"Principal component analysis","volume":"14","author":"Lever","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3784","DOI":"10.1093\/nar\/gkg563","article-title":"ExPASy: The proteomics server for in-depth protein knowledge and analysis","volume":"31","author":"Gasteiger","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"W152","DOI":"10.1093\/nar\/gkl187","article-title":"(PS)2: Protein structure prediction server","volume":"34","author":"Chen","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Chen, C.-C., Hwang, J.-K., and Yang, J.-M. (2009). (PS)2-v2: Template-based protein structure prediction server. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-366"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/15\/7810\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:33:09Z","timestamp":1760164389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/15\/7810"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,22]]},"references-count":62,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22157810"],"URL":"https:\/\/doi.org\/10.3390\/ijms22157810","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,22]]}}}