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Post-transcriptional regulations via small molecules targeting RNA-binding proteins

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Dysregulation of protein–RNA interactions has been associated with various human diseases, while few chemical matters targeting RNA -binding proteins (RBPs) or RNAs are available. In this context, the Wu group investigates small-molecule-based strategies targeting protein–RNA interaction and RNA -binding proteins to offer new chemotypes for the modulation of post-transcriptional regulations. The overall goal is to address the unmet need to investigate the pervasive yet understudied protein–RNA interactions and the associated biological regulatory network, as well as to answer the daunting question regarding the tractability of targeting RNA -binding proteins with new chemical modalities of therapeutic potential. For example, the group has successfully established discovery pipelines for the identification of small molecules that targeted disease-associated RNA -binding proteins involved in RNA biogenesis (LIN28), RNA cleavage and decay (RNase L and IRE1 ), and RNA modification (METTL16 and YTHDF2 ). Furthermore, proximity-inducing bifunctional molecules were studied in the group as chemical probes to illustrate the regulatory mechanism of the complex protein–RNA network or as potential drug candidates for the development of small-molecule-based therapeutics with new mechanisms of action. The talk will exemplify recent small-molecule discovery efforts from the group targeting such RNA -binding proteins.

This talk is part of the Department of Biochemistry - Tea Club Seminars series.

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