Structural Studies of RNA binding proteins that modulate microRNA biogenesis
Nuclear factors 90 and 45 (NF90/NF45) form a complex that recognises dsRNA and is thought to remodel RNA structures. Loss of either protein of these proteins in vertebrates leads to non-viable offspring, suggesting that these proteins are required for an essential step in development. Transcriptome-wide CLIP studies indicate that NF90 recognises some pre-miRNAs, suggesting that the complex may be required for maturation of specific miRNAs.
Previous studies in our laboratory, using X-ray crystallography, have given a detailed insight into how NF90 recognises NF45 and dsRNA. To better understand the architectural changes that occur on RNA binding and how NF90/NF45 interacts with pre-miRNA sequences, the student will characterise these complexes using an integrated structural biology approach. Existing models from crystallographic studies will be combined with cross-linking/mass spectrometry and small angle scattering methods to develop pseudo-atomic models of different NF90/NF45/RNA complexes. These models will help us to develop a mechanistic understanding of miRNA regulation in mammals.
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Nussbacher JK and Yeo GW (2018) Mol. Cell 69:1005
Wolkowicz UM and Cook AG (2012) NAR 40:9356
Jayachandran U, Grey H and Cook AG (2016) NAR 44:1924
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FTE Category A staff submitted: 109.70
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