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Post-transcriptional regulatory networks implicated in the pathophysiological processes of the nervous system

We explore specific and global aspects of post-transcriptional gene regulation mediated by neuronally-enriched and neurodegeneration-associated RNA-binding proteins, microRNAs, tRNA fragments, and circular RNAs to characterize their biological function and uncover novel routes for treating neurodegenerative diseases.

Background

The timing and dosage of gene expression are fundamental determinants of cellular phenotype and organismal complexity. Consequently, the regulation of gene expression is highly coordinated at multiple levels by cis-elements and trans-acting factors. Whereas the specific focus has been on basal transcriptional regulation for many years, post-transcriptional mechanisms regulating RNA metabolism have increasingly emerged as major determinants of gene output. The main reason is mRNA molecules' high sequence plasticity, structural diversity, and agility, making them ideal hubs for partners to bind and modulate protein output in time and space. RNA binding proteins (RBPs) are trans-acting factors that reversibly bind to these mRNAs alone or in conjunction with noncoding RNAs, particularly microRNAs. The transit interaction of RBPs and microRNAs with the mRNA targets results in ribonucleoprotein complexes that determine the fate of mRNAs and, ultimately, the protein sequence, localization, and expression levels.

Research interests

• Delineate the regulatory mechanisms involved in the control of proteins implicated in the pathogenesis of Parkinson's disease.
• Identify RNA biomarkers (microRNA, circRNA, tRNA-fragments) in the blood of patients with Parkinson's disease.
• Elucidate the specific function of neuronal microRNAs, tRNA-fragments, circRNAs, and RNA-binding proteins.
• Test antisense oligonucleotide-based therapies for the treatment of Parkinson's disease.