Exploring molecular mechanisms of RNA-mediated gene regulation
In bacteria, CRISPR systems preserve invading genetic material and incorporate it into surveillance complexes to achieve adaptive immunity. Crystal structures of diverse Cas9 proteins reveal RNA-mediated conformational activation.
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Eukaryotes use a system known as RNA interference, or RNAi, to process host and viral nucleic acid into small interfering RNA (siRNA) or micro-RNA (miRNA) complexes, which then control gene expression. Work in the Doudna lab focuses on miRNA processing.
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The eukaryotic translation machinery is a critical control point for the induction of gene expression. Viruses by necessity hijack the translational equipment. Pictured is the HCV IRES which bypasses normal regulatory mechanisms to promote viral gene expression.
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Doxzen KW, Doudna JA.
PLoS One. 2017 May 17;12(5):e0177097. doi: 10.1371/journal.pone.0177097. eCollection 2017.
Boyle EA, Andreasson JOL, Chircus LM, Sternberg SH, Wu MJ, Guegler CK, Doudna JA, Greenleaf WJ.
Proc Natl Acad Sci U S A. 2017 May 11. pii: 201700557. doi: 10.1073/pnas.1700557114. [Epub ahead of print]
East-Seletsky A, O'Connell MR, Burstein D, Knott GJ, Doudna JA.
NMol Cell. 2017 May 4;66(3):373-383.e3. doi: 10.1016/j.molcel.2017.04.008.
Jiang F, Doudna JA.
Annu Rev Biophys. 2017 Mar 30. doi: 10.1146/annurev-biophys-062215-010822. [Epub ahead of print]
Gaj T, Staahl BT, Rodrigues GM, Limsirichai P, Ekman FK, Doudna JA, Schaffer DV.
Nucleic Acids Res. 2017 Mar 2. doi: 10.1093/nar/gkx154. [Epub ahead of print]