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Madeline Sherlock

Research interests: RNA structure, translation regulation, viral RNA

The Sherlock lab researches how RNAs fold into specific structures that regulate protein synthesis. These RNA structures can regulate translation in terms of the amount of the protein that is produced as well as enabling sequences to be translated that would otherwise be inaccessible to the ribosome. Some of these structures promote expression of proteins encoded by downstream, 3′ end-proximal open reading frames through translation reinitiation. Multiple proteins can be expressed in different quantities from one eukaryotic mRNA through reinitiation. 

Many projects in the lab focus on reinitiation-stimulating RNA structures found in viruses. We strive to understand all aspects of these RNAs, including which viruses contain these reinitiation elements, how they interact with host cell translation machinery, and how sequences from different viruses can cause different levels of expression. Through this research we seek to learn the rules governing RNA structure-function relationships, deepening our understanding of the underlying virology and cellular processes. We will also apply our findings to create biotechnology and therapeutic tools inspired by viral RNA structures. To tackle these research questions, we combine computational approaches with molecular biology, biochemistry, and structural biology methods. This includes homology searches and comparative sequence analysis, reporter RNAs to measure translation, binding assays between viral RNAs and purified cellular components, RNA structure probing, and cryoEM of ribosome complexes.

NCBI bibliography: https://www.ncbi.nlm.nih.gov/myncbi/1-cgxohCGL6A7/bibliography/public/