Functional validation of miRNA variants related to mature miRNA expression levels.

MicroRNAs are one of major mRNA gene expression regulators involved in major cellular processes such as apoptosis, cellular differentiation and cell cycle regulation, but even so, regulation of processes in specific cell types, such as synaptic transmission and synaptogenesis. Changes in miRNA function or expression impact the regulatory ability of miRNAs and lead to the deregulation of mRNA genes important in normal function. Variants located in/or close to the mature miRNA can affect processing of miRNA due to changed secondary transcript structure and/or target selection due to the changes in the seed region. With this project we propose the functional validation of 5 recently identified miRNA variants in 5 distinct miRNA genes using a previously established platform employing SH-SY5Y cells as neuronal model. The miRNA variants were identified by mutation screening using multiplex PCR based, massively parallel sequencing of 66 brain expressed miRNA genes in 1128 psychiatric patients and 1140 controls. The 5 miRNA variants were selected based on a higher frequency in patients as well as predictions based effect on secondary structure of the miRNA transcript. With this project we will be able to investigate the importance of the identified variants in miRNA maturation and at the same time will allow further validation of the established platform for functional analysis of miRNA variants.

Keywords:FUNCTIONAL ANALYSIS, MICRO RNA, NEXT GENERATION SEQUENCING, EXPRESSION STUDIES

Disciplines:Genetics, Systems biology, Molecular and cell biology, Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing