Arlen W JohnsonProfessor
The University of Texas at Austin
Molecular Biosciences, College of Natural Sciences
Austin, TX 78712
Research in Arlen Johnson's Lab
My lab is interested in how cells manufacture ribosomes and ensure that they function correctly for decoding your genome during translation. Since working out the pathway for nuclear export of the large ribosomal subunit more than 10 years ago, we have continued to study both nuclear and cytoplasmic events of making ribosomes (Lo et al Mol Cell, 2010). We have become interested in the general question of how the newly made ribosome is checked for function. We have found that the proper assembly of the P-site, close to the catalytic center of the ribosome, is assessed by several proteins that appear to be mimics of translation factors (Bussiere et al J Cell Bio, 2012). This has led us to propose that the 60S subunit undergoes a "test drive' that involves a pseudo translocation event before it is released into the pool of active ribosomes. We are continuing to pursue this interface between ribosome biogenesis and translation. Ribosomal mutations that disrupt this test drive are associated with Acute T-cell leukemia (De Keersmaecker et al Nat Gen 2013). We are using yeast as a model for these T-ALL mutations to understand the impact of failing in this quality control step. In particular, we are interested in translational fidelity defects caused by these mutations.
In contrast to the large subunit of the ribosome, which catalyzes polypeptide synthesis, the small subunit is responsible for decoding. In a new project in my lab we have shown that the RNA helicase Dhr1 separates U3 snoRNA from the pre-ribosomal RNA to promote folding of the central pseudoknot, a central architetural element that coordinates all domains of the small subunit. Release of U3 and disassembly of the SSU Processome are critical steps for the RNA cleavage that separates the small and large subunits during ribosome assembly. We are currently characterizing the factors that regulate Dhr1 function. We have proposed that Dhr1 is controlled by proteins that assess the status of assembly of the subunit, ensuring that cleavage occurs only after completing the major assembly events of the small subunit.
2014 Sulima SO, Gülay SP, Anjos M, Patchett S, Meskauskas A, Johnson AW, Dinman J, Ekaryotic rpL10 Drives Intrinsic Ribosomal Rotation. Nucleic Acids Res. 42: 2049-63
2014 Sulima SO, Patchett S, Advani VM, de Keersmaecker K, Johnson AW, Dinman J, Bypass of the pre-60S ribosomal quality control as a pathway to oncogenesis. PNAS(USA). 111: 5640-5.
2014 Sardana R, Zhu J, Johnson AW, Physical and functional interactions between the methyltransferase Bud23 and the essential DEAH-box RNA helicase Ecm16. Mol Cell Biol. 34 :2208-2220.
2013 Sardana R, White JP, Johnson AW, The rRNA methyltransferase Bud23 shows functional interaction with components of the SSU processome and RNase MRP, RNA 19: 828-840 view
2013 De Keersmaecker K, Atak ZK, Li N, Vicente C, Patchett S, Girardi T, Gianfelici V, Geerdens E, Clappier E, Porcu M, Lahortiga I, LucÃ R, Yan J, Hulselmans G, Vranckx H, Vandepoel R, Sweron B, Jacobs K, Mentens N, Wlodarska I, Cauwelier B, Cloos J, Soulier J, Uyttebroeck A, Bagni C, Hassan BA, Vandenberghe P, Johnson AW, Aerts S, Cools J., Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia, Nat Gen 48: 186-190 view
2012 Sardana R, Johnson AW, The methyltransferase adaptor protein Trm112 is involved in biogenesis of both ribosomal subunits, MBC 23: 4313-4322 view
2012 Integrity of the P-site is probed during maturation of the 60S ribosomal subunit, Bussiere C, Hashem Y, Arora S, Frank J, Johnson AW., J Cell Bio 197: 747-759 view
2010 J. Sengupta, C. Bussiere, J. Pallesen, M. West, AW. Johnson, and J. Frank, Characterization of the nuclear export adaptor protein Nmd3 in association with the 60S ribosomal subunit, J Cell Biol 189: 1079-1086 view
2010 K.Y. Lo, Z. Li, CBussiere, S. Bresson, EM Marcotte, and AW Johnson, Defining the pathway of cytoplasmic maturation of the 60S ribosomal subunit, Mol Cell 39: 196-208 view
2010 Panse VG, Johnson AW., Maturation of eukaryotic ribosomes: acquisition of functionality, Trends Biochem Sci 35: 260-266 view
2009 Lo KY, Li Z, Wang F, Marcotte EM, Johnson AW, Ribosome stalk assembly requires the dual-specificity phosphatase Yvh1 for the exchange of Mrt4 with P0, J Cell Biol 186: 849-862 view
2009 Li Z, Lee I, Moradi E, Hung NJ, Johnson AW, Marcotte EM, Rational extension of the ribosome biogenesis pathway using network-guided genetics, PLoS Biol 7: 1000213 view
2009 Lo KY, Johnson AW., Reengineering Ribosome Export, Mol Biol Cell 20: 1545-1554 view
2008 Hung NJ, Lo KY, Patel SS, Helmke K, Johnson AW, Arx1 is a nuclear export receptor for the 60S ribosomal subunit in yeast, Mol Biol Cell 19: 734-744
2008 White J, Li Z, Sardana R, Bujnicki JM, Marcotte EM, Johnson AW., Bud23 methylates G1575 of 18S rRNA and is required for efficient nuclear export of pre-40S subunits., Mol Cell Biol 28: 3151-3161 view
2007 Meyer AE, Hung NJ, Yang P, Johnson AW, The specialized cytosolic J-protein, Jjj l, functions in 60S ribosomal subunit biogenesis, PNAS U.S.A. 104: 1558-63
2007 Hedges J, Chen YI, West M, Bussiere C, Johnson AW, Mapping the functional domains of yeast NMD3, the nuclear export adapter for the 60 S ribosomal subunit, J Biol Chem 281: 36579-36587
2007 West M, Hedges JB, Lo KY, Johnson AW, Novel interaction of the 60S ribosomal subunit export adapter Nmd3 at the nuclear pore complex, J Biol Chem 282: 14028-14037
2007 Hofer A, Bussiere C, Johnson AW, Mutational analysis of the ribosomal protein Rpl10 from yeast, J Biol Chem 282: 32630-32639
2006 Hung NJ, Johnson AW, Nuclear recycling of the pre-60S ribosomal subunit-associated factor Arx1 depends on Rei1 in Saccharomyces cerevisiae, Mol Cell Biol 26: 3718-3727
2005 Wang L, Lewis, M, Johnson AW, Domain interactions within the Ski2/3/8 complex and between the Ski complex and Ski7p, RNA 11: 1291-1302
2005 West M, West M, Johnson AW, Defining the order in which Nmd3p and Rpl10p load onto nascent 60S ribosomal subunits, MCB 25: 3802-3813
2005 Hedges J, West M, Johnson AW, Release of the export adapter, Nmd3p, from the 60S ribosomal subunit requires Rpl10p and the cytoplasmic GTPase Lsg1p, EMBO 24: 567-579
2001 Ho H-N, Kallstrom G, Johnson AW, Nmd3p is a Crm1p-dependent adapter protein for nuclear export of the large ribosomal subunit, J Cell Bio 151: 1057-1066