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.
Oh S, Flynn RA, Floor SN, Purzner J, Martin L, Do BT, Schubert S, Vaka D, Morrissy S, Li Y, Kool M, Hovestadt V, Jones DT, Northcott PA, Risch T, Warnatz HJ, Yaspo ML, Adams CM, Leib RD, Breese M, Marra MA, Malkin D, Lichter P, Doudna JA, Pfister SM, Taylor MD, Chang HY, Cho YJ.
Oncotarget 2016 Apr 5
Kaya E, Doxzen KW, Knoll KR, Wilson RC, Strutt SC, Kranzusch PJ, Doudna JA.
Proc Natl Acad Sci U S A 2016 Mar 30
Nelles DA, Fang MY, O'Connell MR, Xu JL, Markmiller SJ, Doudna JA, Yeo GW.
Cell 2016 Mar 16
Nuñez JK, Harrington LB, Doudna JA.
ACS Chem Biol 2016 Feb 9
Jiang F, Taylor DW, Chen JS, Kornfeld JE, Zhou K, Thompson AJ, Nogales E, Doudna JA
Science 2016 Jan 14. pii: aad8282.
Wright AV, Nuñez JK, Doudna JA
Cell 2016 Jan 14;164(1-2):29-44.