The 3' untranslated region of human Cyclin-Dependent Kinase 5 Regulatory subunit 1 contains regulatory elements affecting transcript stability

• Published in: BMC molecular biology 2007-12, Vol.8 (1), p.111-111
• Main Authors: Moncini, Silvia, Bevilacqua, Annamaria, Venturin, Marco, Fallini, Claudia, Ratti, Antonia, Nicolin, Angelo, Riva, Paola
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; 3' Untranslated Regions - metabolism; Cell Differentiation - genetics; Cell Line, Tumor; Cell Movement - genetics; Central Nervous System - growth & development; Central Nervous System - metabolism; Central Nervous System - pathology; Computational biology; ELAV Proteins - genetics; ELAV Proteins - metabolism; Gene Expression Regulation - genetics; Genetic aspects; Genetic regulation; Health aspects; Humans; Intellectual Disability - genetics; Intellectual Disability - metabolism; Intellectual Disability - pathology; Intracellular Signaling Peptides and Proteins - genetics; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - pathology; Neurons - metabolism; Neurons - pathology; Phosphotransferases; RNA Stability - genetics
• ISSN: 1471-2199; 1471-2199
• DOI: 10.1186/1471-2199-8-111

CDK5R1 plays a central role in neuronal migration and differentiation during central nervous system development. CDK5R1 has been implicated in neurodegenerative disorders and proposed as a candidate gene for mental retardation. The remarkable size of CDK5R1 3'-untranslated region (3'-UTR) suggests a role in post-transcriptional regulation of CDK5R1 expression. The bioinformatic study shows a high conservation degree in mammals and predicts several AU-Rich Elements (AREs). The insertion of CDK5R1 3'-UTR into luciferase 3'-UTR causes a decreased luciferase activity in four transfected cell lines. We identified 3'-UTR subregions which tend to reduce the reporter gene expression, sometimes in a cell line-dependent manner. In most cases the quantitative analysis of luciferase mRNA suggests that CDK5R1 3'-UTR affects mRNA stability. A region, leading to a very strong mRNA destabilization, showed a significantly low half-life, indicating an accelerated mRNA degradation. The 3' end of the transcript, containing a class I ARE, specifically displays a stabilizing effect in neuroblastoma cell lines. We also observed the interaction of the stabilizing neuronal RNA-binding proteins ELAV with the CDK5R1 transcript in SH-SY5Y cells and identified three 3'-UTR sub-regions showing affinity for ELAV proteins. Our findings evince the presence of both destabilizing and stabilizing regulatory elements in CDK5R1 3'-UTR and support the hypothesis that CDK5R1 gene expression is post-transcriptionally controlled in neurons by ELAV-mediated mechanisms. This is the first evidence of the involvement of 3'-UTR in the modulation of CDK5R1 expression. The fine tuning of CDK5R1 expression by 3'-UTR may have a role in central nervous system development and functioning, with potential implications in neurodegenerative and cognitive disorders.