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SUMMARY OF RESEARCH
Summary
The tightly regulated process of precursor messenger RNA (pre-mRNA) alternative splicing is a key mechanism to increase the number and complexity of proteins encoded by the genome. The results of deep sequencing-based expression analyses suggest that more than 90% of multi-exon human genes undergo alternative splicing. Changes in the cis- or trans- regulation of this process can cause multiple pathologies as a result of general or specific aberrant pre-mRNA processing underscoring the fundamental importance of this regulatory process. Evidence gathered in recent years has established that transcription and splicing are physically and functionally coupled and that this coupling may be an essential aspect of the regulation of splicing and alternative splicing.
Despite considerable efforts, numerous questions remain regarding the functional significance and global impact of this coupling on cellular and organism homeostasis as well as its underlying molecular mechanisms. In addition to study the molecular events that govern the interactions between the transcription and splicing machineries, we want to go further and provide new insights regarding the molecular mechanisms at work in pathological situations. Our research aims to elucidate the mechanisms of transcription and pre-mRNA processing regulation, which may provide novel and important insights regarding the molecular events that lead to neurological and lymphoproliferative disorders. We also want to identify and characterize the cellular components of these important pathways that should set the groundwork for the understanding of their functions. It is very likely that as this is achieved we will also learn valuable lessons on novel transcriptional/alternative splicing regulatory mechanisms of cellular genes.
1. Transcription/alternative splicing regulation in nervous system
We study the function of WW- and FF-containing proteins in neurogenesis and investigate the molecular mechanism/s by which these factors are affecting the transcription/alternative splicing of endogenous mRNAs that may contribute to the disease phenotype in neurological disorders.
2. Transcription/alternative splicing regulation in cancer
We study the link between the transcription/alternative splicing activity of core spliceosome machinery and the development of haematological malignancies.
We are also starting research lines to study the regulation of pre-mRNA splicing in DNA repair, which is essential to maintain genome integrity, to offer new insights into the mechanism of neoplastic transformation.
3. Transcription/alternative splicing regulation in living cells
We investigate the spatial organization and dynamics of transcription and pre-mRNA processing within the highly compartmentalized eukaryotic nucleus, which are fundamental to fully understand how the regulation of gene expression is exerted in the cell.
FUNDING AGENCIES LAST 5 YEARS
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