title: Identification of antisense long noncoding RNAs that function as SINEUPs in human cells.
abstract: Mammalian genomes encode numerous natural antisense long noncoding RNAs (lncRNAs) that regulate gene expression. Recently, an antisense lncRNA to mouse Ubiquitin carboxyl-terminal hydrolase L1 (Uchl1) was reported to increase UCHL1 protein synthesis, representing a new functional class of lncRNAs, designated as SINEUPs, for SINE element-containing translation UP-regulators. Here, we show that an antisense lncRNA to the human protein phosphatase 1 regulatory subunit 12A (PPP1R12A), named as R12A-AS1, which overlaps with the 5' UTR and first coding exon of the PPP1R12A mRNA, functions as a SINEUP, increasing PPP1R12A protein translation in human cells. The SINEUP activity depends on the aforementioned sense-antisense interaction and a free right Alu monomer repeat element at the 3' end of R12A-AS1. In addition, we identify another human antisense lncRNA with SINEUP activity. Our results demonstrate for the first time that human natural antisense lncRNAs can up-regulate protein translation, suggesting that endogenous SINEUPs may be widespread and present in many mammalian species.
authors.affiliation: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, RIKEN Yokohama Campus, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 Japan.|Center for RNA Medicine, Department of Clinical Medicine, Aalborg University Campus Copenhagen, Copenhagen 2450 Denmark.
authors.forename: Aleks
authors.initials: A
authors.lastname: Schein
authors.affiliation: Scuola Internazionale Superiore di Studi Avanzati, Area of Neuroscience, Trieste, Italy.|Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Zucchelli
authors.affiliation: Center for RNA Medicine, Department of Clinical Medicine, Aalborg University Campus Copenhagen, Copenhagen 2450 Denmark.
authors.forename: Sakari
authors.initials: S
authors.lastname: Kauppinen
authors.affiliation: Scuola Internazionale Superiore di Studi Avanzati, Area of Neuroscience, Trieste, Italy.|Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gustincich
authors.affiliation: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, RIKEN Yokohama Campus, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 Japan.
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
mesh_terms: D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D006801:Humans; D043263:Myosin-Light-Chain Phosphatase / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human