title: A long non-coding RNA, BC048612 and a microRNA, miR-203 coordinate the gene expression of neuronal growth regulator 1 (NEGR1) adhesion protein.
abstract: The regulatory roles for non-coding RNAs, the long non-coding RNAs and microRNAs, are emerging as crucial determinants of central nervous system development and function. Neuronal growth regulator 1 (NEGR1) is a cell adhesion molecule that has been shown to play an important role in neurite outgrowth during neuronal development. Precise expression of the Negr1 gene is crucial for proper brain development and is dysregulated during brain injury. Hence, we attempted to elucidate the non-coding RNAs that control Negr1 gene expression. A long non-coding RNA, BC048612, transcribed from the bidirectional GC-rich Negr1 gene promoter was found to influence Negr1 mRNA expression. In vitro knockdown of the long non-coding RNA resulted in significant down-regulation of Negr1 mRNA expression, NEGR1 protein levels and neurite length whereas over-expression enhanced Negr1 mRNA expression, NEGR1 protein levels and increased neurite length. Meanwhile, another non-coding RNA, microRNA-203, was found to target the 3' untranslated region of the Negr1 mRNA. Inhibition of microRNA-203 led to increased expression of Negr1 mRNA, elevated NEGR1 protein levels and increased neurite length. Conversely, microRNA-203 over-expression decreased the level of Negr1 mRNA, NEGR1 protein and neurite length. Neither microRNA-203 nor the long non-coding RNA, BC048612 could influence each other's expression. Hence, the long non-coding RNA, BC048612, and microRNA-203 were determined to be positive and negative regulators of Negr1 gene expression respectively. These processes have a direct effect on NEGR1 protein levels and neurite length, thus highlighting the importance of the regulatory non-coding RNAs in modulating Negr1 gene expression for precise neuronal development.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, 117597, Singapore.
authors.forename: Prameet
authors.initials: P
authors.lastname: Kaur
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, 117597, Singapore.
authors.forename: Jun Rong
authors.initials: JR
authors.lastname: Tan
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, 117597, Singapore.
authors.forename: Dwi Setyowati
authors.initials: DS
authors.lastname: Karolina
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, 117597, Singapore.
authors.forename: Sugunavathi
authors.initials: S
authors.lastname: Sepramaniam
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, 117597, Singapore.
authors.forename: Arunmozhiarasi
authors.initials: A
authors.lastname: Armugam
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, 117597, Singapore.
authors.forename: Peter T-H
authors.initials: PT
authors.lastname: Wong
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, 117597, Singapore.; Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria 3800, Australia. Electronic address: bchjeya@nus.edu.sg.
authors.forename: Kandiah
authors.initials: K
authors.lastname: Jeyaseelan
mesh_terms: D000818:Animals; D001483:Base Sequence; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D008969:Molecular Sequence Data; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000502:physiology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C575934:MIRN203 microRNA, mouse; D035683:MicroRNAs; C000592528:NEGR1 protein, mouse; D062085:RNA, Long Noncoding
keywords: Cell adhesion molecules; Negr1; Neuronal maturation; Non-coding RNA; lncRNA; miRNA