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.
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.
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.
Lee AS, Kranzusch PJ, Doudna JA, Cate JH.
Nature. 2016 Jul 27. doi: 10.1038/nature18954. [Epub ahead of print]
Carlson LA, Bai Y, Keane SC, Doudna JA, Hurley JH.
Elife 2016 Jun 25;pii: e14663. doi: 10.7554/eLife.14663. [Epub ahead of print]
Nuñez JK, Bai L, Harrington LB, Hinder TL, Doudna JA.
Mol Cell 2016 Jun 16;62(6):824-33.
Oakes BL, Nadler DC, Flamholz A, Fellmann C, Staahl BT, Doudna JA Savage DF.
Nat Biotechnol. 2016 Jun;34(6):646-51.
Isaac RS, Jiang F, Doudna JA, Lim WA, Narlikar GJ, Almeida RA
Elife 2016 Apr 28;5. pii: e13450.
Nelles DA, Fang MY, O'Connell MR, Xu JL, Markmiller SJ, Doudna JA, Yeo GW
Cell 2016 Apr 7;165(2):488-96.