Data di Pubblicazione:
2007
Citazione:
The human CDK5R1 3'UTR contains distinct subregions affecting transcript stability / S. Moncini, M. Venturin, A. Bevilacqua, A. Ratti, A. Nicolin, P. Riva. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1018-4813. - 15:Suppl. 1(2007), pp. 308-308. ((Intervento presentato al convegno European Human Genetics Conference tenutosi a Nice (France) nel 2007.
Abstract:
Human CDK5R1 encodes for p35, a neurone-specific activator of
CDK5, which is involved in neuronal migration and differentiation
during CNS development. CDK5R1 has been implicated in neurodegenerative
disorders and proposed as a candidate gene for mental
retardation. The remarkable size of CDK5R1 3’UTR suggests a role
of this region in the control of CDK5R1 expression by post-transcriptional
regulatory elements modulating mRNA stability or translation efficiency.
Bioinformatic analysis showed a high conservation degree in
mammals and predicted several AU-Rich Elements (AREs). CDK5R1
3’UTR was cloned in pGL4.71 at the 3’ end of the Renilla luciferase reporter
gene to perform Dual Luciferase assays: the construct showed
a decreased luciferase activity in six transfected cell lines. The quantitative
analysis of luciferase mRNA suggests that CDK5R1 3’UTR affects
mRNA stability. We identified five 3’UTR subregions reducing the
luciferase activity in some instance with a cell line-dependent way. A
region showed a significantly low halflife, suggesting an accelerated
mRNA degradation. We also identified, by deletion analysis, a type I
ARE displaying a stabilizing effect in two neuroblastoma cell lines. Our
findings evince the presence of both destabilizing and stabilizing regulatory
elements in CDK5R1 3’UTR. We are now attempting to identify,
by REMSA and immunoprecipitation assays, stabilizing neuronal proteins
that specifically bind the type I ARE, with the final aim of verifying
the functionality of this element. The fine tuning of CDK5R1 expression
by 3’UTR may play a role in CNS development and functioning, with
potential implications in neurodegenerative and cognitive disorders.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
S. Moncini, M. Venturin, A. Bevilacqua, A. Ratti, A. Nicolin, P. Riva
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