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- Title
Complex CDKL5 translational regulation and its potential role in CDKL5 de?ciency disorder.
- Authors
Ruggiero, Valeria; Fagioli, Claudio; de Pretis, Stefano; Di Carlo, Valerio; Landsberger, Nicoletta; Zacchetti, Daniele
- Abstract
CDKL5 is a kinase with relevant functions in correct neuronal development and in the shaping of synapses. A decrease in its expression or activity leads to a severe neurodevelopmental condition known as CDKL5 deficiency disorder (CDD). CDD arises from CDKL5 mutations that lie in the coding region of the gene. However, the identification of a SNP in the CDKL5 5'UTR in a patient with symptoms consistent with CDD, together with the complexity of the CDKL5 transcript leader, points toward a relevant translational regulation of CDKL5 expression with important consequences in physiological processes as well as in the pathogenesis of CDD. We performed a bioinformatics and molecular analysis of the 5'UTR of CDKL5 to identify translational regulatory features. We propose an important role for structural cis-acting elements, with the involvement of the eukaryotic translational initiation factor eIF4B. By evaluating both cap-dependent and cap-independent translation initiation, we suggest the presence of an IRES supporting the translation of CDKL5 mRNA and propose a pathogenic effect of the C>T -189 SNP in decreasing the translation of the downstream protein.
- Subjects
SINGLE nucleotide polymorphisms; GENETIC code
- Publication
Frontiers in Cellular Neuroscience, 2023, p01
- ISSN
1662-5102
- Publication type
Article
- DOI
10.3389/fncel.2023.1231493