Karen S. Browning
Mechanism and Regulation of Eukaryotic Protein Synthesis
My research focuses on the initiation of protein synthesis in higher plants. We are seeking a molecular description of the process in which initiation factors (eIF4A, eIF4B, eIF4F, eIF3, eIF2 and PABP) select, prepare and bind messenger RNA to the 40S ribosome. Plants have a unique second form of eIF4F (eIF(iso)4F), and we are using a variety of methods (genetic knockouts, gene silencing, DNA arrays, etc.) to discover the function of this novel initiation factor. We are also interested in the features of messenger RNAs that make some messenger RNAs translate more efficiently than others and why plants need two forms of eIF4F. We are studying a plant viral RNA, satellite tobacco necrosis virus, that appears to use a region in the 3’ untranslated region (3’ UTR) to facilitate cap-independent translation by recruiting eIF4F. eIF4F is normally bound to the 5’ cap of mRNAs during initiation, so the use of the viral 3’ UTR to facilitate initiation at the 5’ end represents a novel mechanism. We are using a variety of techniques to study the interactions of initiation factors with each other and with messenger RNAs (expression of cloned factors, site-directed mutagenesis, crystallography, yeast three-hybrid system, fluorescence, etc.). From our studies we hope to gain a better understanding of the protein-protein and protein-RNA interactions that must occur for successful initiation of translation of a specific messenger RNA to occur.
Visit the FIAT Database for more information about Arabidopsis Translation Factors
Roberts, R., Mayberry, L.K., Browning, K.S., Rakotondrafara, A.M. (2017) The Triticum Mosaic Virus 5' Leader Binds to Both eIF4G and eIFiso4G for Translation. PLoS One 12:e0169602.
Levins, E., Tseng, C.Y., Patrick, R.M., Mayberry, L.K., Cole, N., Browning, K.S. (2016) Fusion proteins of Arabidopsis cap-binding proteins: Cautionary "tails" of woe. Translation (Austin) 4:e1257408.
Bush, M.S., Pierrat, O., Nibau, C., Mikitova, V., Zheng, T., Corke, F.M., Vlachonasios, K., Mayberry, L.K., Browning, K.S., Doonan, J.H. (2016) eIF4A RNA Helicase Associates with Cyclin-Dependent Protein Kinase A in Proliferating Cells and is Modulated by Phosphorylation. Plant Physiol. 172:128-40.
Browning KS, Bailey-Serres J. Mechanism of cytoplasmic mRNA translation. Arabidopsis Book.(2015)13:e0176.
Patrick, R.M., Mayberry, L.K., Choy, G., Woodard, L.E., Liu, J.S., White, A., Mullen, R.A.,Tanavin, T.M., Latz, C.A. and Browning, K.S. (2014) Two Arabidopsis thaliana loci encode novel eIF4E isoforms that are functionally distinct from the conserved plant eIF4E. Plant Phys 164: 1820-30
O’Brien, J.P., Mayberry, L.K., Murphy, P.A., Browning, K.S. and Brodbelt, J.S. (2013) Evaluating the Conformation and Binding Interface of Cap Binding Proteins and Complexes via Ultraviolet Photodissociation Mass Spectrometry. J Proteome Res. 12(12):5867-77
Patrick, R.M. and Browning, K.S. (2012) The eIF4F and eIFiso4F Complexes of Plants: An Evolutionary Perspective. Comp Funct Genomics. 2012:287814
Mayberry,L.K., Allen, M.L., Nitka, K.R., Campbell, L., Murphy, P.A. and Browning, K.S. (2011) Plant cap binding complexes eukaryotic initiation factors eIF4F and eIFiso4F: Molecular specificity of subunit binding. J. Biol. Chem. 286:42566-74.
Lellis AD, Allen ML, Aertker AW, Tran JK, Hillis DM, Harbin CR, Caldwell C, Gallie DR, Browning KS (2010) Deletion of the eIFiso4G subunit of the Arabidopsis eIFiso4F translation initiation complex impairs health and viability" Plant Mol Biol 74:249-63.