Accuracy and Efficiency of Protein Synthesis Elongation in Escherichia coli

The translation process can be perturbed during the elongation phase. "Recoding" events utilize signals embedded in certain messenger RNAs which reprogram ribosomes to shift reading frames or read through stop codons, among other unexpected behaviors. The efficiency of the translation process is also subject to variability depending on levels of uncharged tRNAs, as well as the codon composition, structure, and stability of mRNAs. Codon utilization among synonym codons varies widely from organism to organism, and between highly expressed and poorly expressed genes in the same organism. This laboratory has focused on effects of uncharged tRNA, translational frameshifts and other recoding events, and effects of codon bias in Escherichia coli. In earlier work, we showed in vivo that uncharged tRNA can affect translation by entering the ribosomal "A" site, with implications for how the "stringent response" occurs. With respect to translational frameshifts, we have provided strong evidence for a model in which +1 (rightward) translational frameshifts are governed by the speed of the ribosome and the extent of vacancy of the A site. With respect to codon bias, we have developed a vector system for assessing the influence of rare codons on translation, and have shown that both consecutive rare arginine and rare leucine codons significantly inhibit expression at the translational level. We have reported an unexplained new finding, termed "5' translational blockage," in which consecutive low-usage codons show much greater inhibition of translation when they are located near the translation start site compared to the middle of the gene.

• Goldman E, and Green L. (editors) (2009) Practical Handbook of Microbiology, Second Edition, CRC Press, Boca Raton, FL (853 pages)
• Goldman E (2008) Translation Control by RNA [revised]. In: Encyclopedia of Life Sciences, John Wiley & Sons, Ltd: Chichester UK (13 pages), http://www.els.net
• Goldman E (2008) Transfer RNA [revised]. In: Encyclopedia of Life Sciences, John Wiley & Sons, Ltd: Chichester UK (11 pages) http://www.els.net
• Goldman E (2007) Translation Control by Proteins [revised]. In: Encyclopedia of Life Sciences, John Wiley & Sons, Ltd: Chichester UK (9 pages) http://www.els.net[doi:10.1002/9780470015902.a0000860.pub2]
• Shu P, Dai H, Gao W, Goldman E. (2006) Inhibition of translation by consecutive rare leucine codons in E. coli: Absence of effect of varying mRNA stability. Gene Expression 13: 97-106.
• Shu P, Dai H, Mandecki W, Goldman E. (2004) CCC CGA is a Weak Translational Recoding Site in Escherichia coli. Gene 343:127-132
• Song L, Mandecki, W and Goldman, E., 2003, Expression of non-open reading frames isolated from phage display due to translation reinitiation. FASEB J. 17:1674-1681.
• Cheng, L. and Goldman, E., 2001, Absence of effect of varying Thr-Leu codon pairs on protein synthesis in a T7 system. Biochemistry 40:6102-6106.
• Goldman, E., Korus, M. and Mandecki, W., 2000, Efficiencies of translation in three reading frames of unusual non-ORF sequences isolated from phage display. FASEB J. 14:603-611.

Honors

At Brandeis: Sara Chaitt Memorial Scholarship; Chemistry Department Prize, May, 1966

Damon Runyon Fellow, 1972-74

Lievre Senior Fellow, CA Div. American Cancer Society, 1977-79

Research Career Development Award, National Cancer Institute, 1983-88

Member, American Cancer Society "Genetic Mechanisms in Cancer" Study Section, 1998-2002

Editorial Board, Protein Expression and Purification, 1996-present

Elected President, Amer. Assoc. Univ. Prof.-UMDNJ chapter, 1997; re-elected, 1998

Awarded "Basic Science Faculty of the Year" by the NJMS Faculty Organization, 2000

Elected Vice-President (2003-4) and President (2004-5) of the NJMS Faculty Organization

Editorial Board, Applied and Environmental Microbiology, 2011-2014

Training and Positions

1966 B.A. cum laude, Brandeis University, Waltham, MA

1972 Ph.D. in Biochemistry, M.I.T., mentor: Harvey Lodish, Cambridge, MA

1972-73 Postdoctoral fellow in Viral Oncology, PHRI, NY, NY, mentor: Tom Benjamin

1973-75 Postdoctoral fellow in Pathology, Harvard Medical School, Boston, MA, mentor: Tom Benjamin

1975-77 Postdoctoral fellow in Microbiology, Univ. California, Irvine, mentor: G. Wesley Hatfield

1977-79 Assistant Research Microbiologist, Univ. California, Irvine

1979-present Asst. Prof. to Assoc. Prof. (1983) to Professor (1993), Microbiology & Mol. Genet., (Legacy UMDNJ-NJMS) New Jersey Medical School, Rutgers, The State University of New Jersey

1990-91 Sabbatical, Dept. of Biology, Brookhaven National Laboratory, NY, mentor: F.W. Studier