Identification and functional characterization of trans-acting factors involved in the post-transcriptional regulation of CDK5R1
Abstract
Data di Pubblicazione:
2012
Citazione:
Identification and functional characterization of trans-acting factors
involved in the post-transcriptional regulation of CDK5R1 / P. Zuccotti, A. Barbieri, C. Colombrita, S. De Palma, S. Moncini, C. Gelfi, A. Ratti, M. Venturin, P. Riva. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1018-4813. - 20:suppl.1(2012), pp. 262-262. ((Intervento presentato al convegno European Human Genetics Conference in conjunction with the European Meeting on Psychosocial Aspects of Genetics and the
German Society of Human Genetics tenutosi a Nürnberg nel 2012.
Abstract:
CDK5R1 encodes p35, an activator of CDK5, a proline-directed serine/threonine
kinase that phosphorylates proteins involved in CNS development and
maintenance. CDK5 and p35 were found to show an important role in neuronal
migration and differentiation during CNS development and were also
implicated in some neurodegenerative and cognitive disorders. Both the
CDK5R1 3’-UTR remarkable size and its conservation during the evolution
are strongly indicative of an important function in post-transcriptional regulation.
We recently reported that CDK5R1 3’-UTR contains regulatory elements
affecting transcript stability. In particular, a 138 bp region, that does
not contain known miRNA binding sites, has been identified as the most
destabilizing portion of the 3’-UTR by luciferase assays. UV cross-linking
and site directed mutagenesis experiments allowed us to delimit potential
binding site for RNA binding proteins (RBPs), among which we identified
the nELAVs, showing a stabilizing activity on CDK5R1 transcript after overexpression
and silencing experiments. To search for putative destabilizing
factors, pull-down experiments have been carried out, allowing us to identify
further binding factors, among which hnRNPA2/B1. The validation of
hnRNPA2/B1 binding and the study of its silencing/over-expression might
help to disclose the possible role of this protein on CDK5R1 post-transcriptional
regulation.
This study will help to define the functional role of the gene, addressing studies
on the CDK5R1 implication in the pathogenesis of neurodegenerative
and cognitive diseases.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
P. Zuccotti, A. Barbieri, C. Colombrita, S. De Palma, S. Moncini, C. Gelfi, A. Ratti, M. Venturin, P. Riva
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