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Non-coding RNAs in neural circuit development and disease

Non-coding RNAs play a crucial role in neural development and disease. We focus on different classes of non-coding RNAs: for example, microRNAs (miRNAs), circular RNAs (circRNAs) and transfer RNA fragments (tRFs). miRNAs are small non-coding RNAs (22 nt) that bind specific mRNA targets thereby regulating their translation and stability. Deregulation of miRNAs has been implicated in various brain disorders and these molecules are considered to be promising therapeutic targets in many of these disorders. . We study the role of miRNAs in the pathogenesis of different neurological diseases and explore the therapeutical potential of miRNAs in ALS.

For example, our previous work shows that miRNAs are deregulated at different levels in patients suffering from temporal lobe epilepsy (TLE) and using a multidisciplinary approach (e.g. RNAseq, biotinIP, in vivo Ago IPs, epilepsy models etc) we deciphered how miRNAs contribute to the process of epileptogenesis and how these effects can be reversed. Circular RNAs are a recently (re)discovered class of long non-coding RNAs with a circular structure. circRNAs are enriched in the brain and in specific subcellular compartments in neurons and due to their circular structure very stable. Some circRNAs can act as miRNA sponges while the function of most other circRNAs remains to be determined.

We aim to determine which circRNAs are important for axonal development and how they affect this process. Similarly, we study deregulated circRNAs in neurological diseases. Fragments derived from tRNAs are implicated in different aspects of gene regulation. For example, some tRFs can function as miRNAs. We study the role of tRFs in neural circuit development and disease.

This work is in part supported by EpilepsieNL, Stichting ALS Nederland and Health Holland. Furthermore, part of this work is performed in close collaboration with InteRNA Technologies.