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Johns Hopkins University logoProgram in Molecular Biophysics
Rachel Green 

Rachel Green

Professor
Department of Molecular Biology and Genetics
School of Medicine


B.S. 1986, University of Michigan
Ph.D. 1992, Harvard University

ragreen@jhmi.edu

702A PCTB
725 N. Wolfe Street
Baltimore, MD 21205

Office: 410-614-4922
Lab: 410-614-492
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The growth and viability of an organism depends upon the fast and faithful decoding of that organism’s genomic information into functional peptide sequences. High-accuracy protein synthesis helps to ensure that miscoded polypeptides are not produced, as errant polypeptides are prone to misfold and may have undesirable toxic consequences in the cell. The overall fidelity and productivity of protein synthesis is dictated by the action of the ribosome. During each cycle of translation elongation, the ribosome carefully selects the appropriate aminoacyl-tRNA (aa-tRNA) from a large competing pool. The selected aa-tRNA carries the amino acid that matches the mRNA codon currently in the ribosome’s decoding center, and is the only aa-tRNA permitted to enter the ribosome and incorporate a new amino acid onto the growing polypeptide chain. Similarly, during termination, the ribosome permits only protein release factors to enter the ribosome where they stimulate release of the nascent peptide. Moreover, when there are problems during elongation and termination, the ribosome is centrally involved in triggering "rescue" responses that target the mRNA and incomplete protein products for degradation, as well as rescuing the ribosomes for subsequent rounds of translation. These so called "mRNA surveillance" systems exist in both bacteria and eukaryotes, but are very distinct from one another. We are interested in understanding the molecular mechanisms through which the ribosome imposes high fidelity on the normal processes of tRNA selection and termination, as well as the molecular mechanisms through which translational irregularities are recognized and dealt with. We couple biochemical (usually bulk pre-steady state) approaches with ribosome profiling (a high throughput sequencing-based genomic approach) to define these mechanisms. Recent studies have identified biochemical roles for key components in the mRNA surveillance pathways including Dom34, Hbs1, Rli1 and Upf1. Ongoing efforts continue to dissect these pathways with increasing interest in relevance to diseases in eukaryotes related to ribosome deficiencies (ribosomopathies).


Selected Publications

Koutmou, K.S., Schuller, A.P., Brunelle, J.L., Radhakrishnan, A., Djuranovic, S., and R. Green. (2015) Ribosomes slide on lysine-encoding homopolymeric A stretches. eLife, 10.7554/eLife.05534. PMCID: PMC4363877

Woostenhulme, D.J., Guydosh, N.R., Green, R., and A.R. Buskirk. (2015) High Precision Analysis of Translational Pausing by Ribosome Profiling in Bacteria Lacking EFP. Cell Reports 11:13-21
 
Young, D., Guydosh, N.R., Zhang, F., Hinnebusch, A.G., and R. Green. (2015) Rli1/ABCE1 recycles terminating ribosomes and controls reinitiation in 3’ UTRs in vivo. Cell 162:872-84. PMCID: PMC4556345
 
Guydosh, N., and R. Green. (2014) Dom34 rescues ribosomes in 3’ untranslated regions. Cell 156:950-62. PMID: 24581494. PMCID: PMC4022138
 
Djuranovic, S., Nahvi, A., and R. Green. (2012) miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay. Science 336:237-40.  PMID: 22499947. PMCID: PMC3971879
 
Shoemaker, C.J., and R. Green (2011). Kinetic analysis reveals the ordered coupling of translation termination and ribosome recycling in yeast. Proc Natl Acad Sci USA 108:E1392-8. PMCID: PMC3251084

Zaher, H.S, and R. Green (2011). A primary role for release factor 3 in quality control during translation elongation in Escherichia coli. Cell 147:396-408. PMCID: 3415990

Shoemaker, C.J., D.E. Eyler, and R. Green. (2010) Dom34:Hbs1 promotes subunit dissociation and peptidyl-tRNA drop off to initiate no-go decay. Science 330:369-372.

Zaher, H.S., and R. Green. (2010) Hyperaccurate and error-prone ribosomes exploit distinct mechanisms during tRNA selection. Mol. Cell 39:110-120.

Zaher, H.S., and R. Green. (2009) Quality control by the ribosome following peptide bond formation. Nature 457:161-166. 

Cochella, L., Brunelle, J., and R. Green. (2007) Mutational analysis reveals two independent molecular requirements during transfer RNA selection on the ribosome. Nat Struct Mol Biol 14:30-6. PMCID: no number 

Cochella, L., and R. Green. (2005) An active role for tRNA in decoding beyond codon:anticodon pairing. Science 308: 1178-80. PMCID: PMC1687177 

Youngman, E.M., Brunelle, J.L., Kochaniak, A.B., and R. Green. (2004) The active site of the ribosome is composed of two layers of conserved nucleotides with distinct roles in peptide bond formation and peptide release. Cell 117: 589-99. PMCID: no number

 

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