Rebecca Alexander

Education

B.S., University of Delaware, 1990, Honors
PhD, University of Pennsylvania, 1996, (Barry S. Cooperman)
Postdoctoral Research Associate 1996-1997, MIT, (Paul Schimmel)
Postdoctoral Research Associate 1997-1999, The Scripps Research Institute, (Paul Schimmel)

Research Description

Our research program is centered on tRNA-acting enzymes. Translation of a single protein from its nucleic acid precursor requires dozens of cellular components. Amino acids are assembled into polypeptides at the ribosome, a large ribonucleoprotein complex where the genetic message is decoded. Individual proteins play essential roles in maintaining the accuracy of translation. The aminoacyl-tRNA synthetases attach amino acids to transfer RNA (tRNA) molecules, thereby establishing the genetic code that dictates which amino acid matches which trinucleotide codon. tRNA modifying enzymes expand the nucleotide alphabet and can alter the structure, dynamics, or decoding properties of tRNAs.

Publications

Muraski M, Nilsson E, Fritz, MJ, Richardson, AR, Alexander RW, and Copper, VC. (2023) Adaptation to overflow metabolism by mutations that impair tRNA modification in experimentally evolved bacteria. mBio in press.

Muraski M, Nilsson E, Weekley B, Sharma SB, Alexander RW. (2020) A novel aminoacyl-tRNA synthetase appended domain can supply the core synthetase with its amino acid substrate. Genes 11:1320-1331.

Godwin, R.C., Macnamara, L.M., Alexander, R.W., and Salsbury, F.R. Jr. (2018) Structure and dynamics of tRNA^Met containing core substitutions. ACS Omega 3: 10668–10678.

Jones, TE, Ribas de Pouplana, L, and Alexander, RW. (2013) Evidence for late resolution of the AUX codon box in evolution. J. Biol. Chem. 288:19625-19632.  

Banerjee R., Reynolds N.M., Yadavalli S.S., Rice C., Roy H., Banerjee P., Alexander R.W., Ibba M. Banerjee R., Reynolds N.M., Yadvalli. S.S., Roy H., Banerjee P., Alexander R.W., Ibba M. (2011) Mitochondrial aminoacyl-tRNA synthetase single-nucleotide polymorphisms that lead to defects in refolding but not aminoacylation. J. Mol. Biol. 410: 280-293.

Jones T.E., Alexander R.W., Pan T. (2011) Misacylation of specific nonmethionyl tRNAs by a bacterial methionyl-tRNA synthetase. Proc. Natl. Acad. Sci. USA 108: 6933-6938.

Casina, V.C., Lobashevsky, A.A., McKinney, W.E., Brown, C.L., and Alexander, R.W. (2011) Role for a conserved structural motif in assembly of a class I aminoacyl-tRNA synthetase active site. Biochemistry 50: 763-769.

Alexander, RW, Eargle, J, and Luthey-Schulten, Z (2010) Experimental and computational determination of tRNA dynamics. FEBS Letters 584: 376-386.

Banerjee, P, Warf, M.B., and Alexander, R.W. (2009) Effect of a domain-spanning disulfide on aminoacyl-tRNA synthetase activity. Biochemistry 48: 10113-10119.

Jones, T.E., Brown, C.L, Geslain, R., Alexander, R.W. and Ribas de Pouplana, L. (2008) An operational RNA code for faithful assignment of ATG triplets to methionine. Molecular Cell 29: 401-407.

Budiman, M.E., Knaggs, M.H., Fetrow, J.S., and Alexander, R.W. (2007) Using molecular dynamics to map interaction networks in an aminoacyl-tRNA synthetase.  Proteins: Structure, Function, and Bioinformatics 68: 670-689.

Turner, A.W., Love, C., Alexander, R.W., and Jones, P.G. (2007) Mutational analysis of E. coli DEAD-box protein CsdA.  Journal of Bacteriology 189:2769-2776.

M.E. Budiman, U. Bierbach, and R.W. Alexander (2005) “DNA minor groove adducts formed by a platinum-acridine conjugate inhibit association of TATA-binding protein with its cognate sequence.” Biochemistry44, 11262-11268.

M.E. Budiman, R.W. Alexander, and U. Bierbach (2004) “Unique base-step recognition by a platinum-acridinylthiourea conjugate leads to a DNA damage profile complementary to that of the anticancer drug cisplatin.” Biochemistry43, 8560-8567.

R.W. Alexander, and K. Tamura (2004) “Peptide synthesis through evolution.” Cell. Mol. Life Sci.61, 1317-1330.

R.W. Alexander, and P. Schimmel (2001) “Domain-domain communication in aminoacyl-tRNA synthetases.” Prog. Nucl. Acid Res. Mol. Biol. 69, 317-349.

R.W. Alexander and P. Schimmel (2002) “Protein synthesis.” In Encyclopedia of Physical Science and Technology (Robert A. Myers, ed.)  3 rd ed., Vol. 13. Academic Press ( San Diego, CA), 219-240.

R.W. Alexander and P. Schimmel (2000) “Multifunctional proteins.” In McGraw-Hill 2001 Yearbook of Science & Technology, McGraw-Hill ( New York, NY), pp.265-266.

B. S. Cooperman, R. W. Alexander, Y. Bukhtiyarov, S. N. Vladimirov, Z. Druzina, R. Wang, and N. Zuno (2000) “Photolabile derivatives of oligonucleotides (PHONTs) as probes of ribosomal structure.” Methods Enzymol. 318, 118-136.

R.W. Alexander and P. Schimmel (1999)  “Evidence for breaking domain-domain functional communication in a synthetase-tRNA complex.” Biochemistry38, 16359-16365.

R. Wang, R.W. Alexander, M. van Loock, S. Vladimirov, Y. Bukhtiyarov, S.C. Harvey, and B.S. Cooperman (1999) “Three-dimensional placement of the conserved 530 loop of 16 S rRNA and of its neighboring components in the 30 S subunit.” J. Mol. Biol. 286, 521-540.

R.W. Alexander, B.E. Nordin, and P. Schimmel (1998) “Activation of microhelix charging by localized helix destabilization.” Proc. Natl. Acad. Sci. USA95, 12214-12219.

P. Schimmel and R.W. Alexander (1998) “Diverse RNA substrates for aminoacylation: clues to origins?” Proc. Natl. Acad. Sci. USA 95, 10351-10353.

P. Schimmel and R.W. Alexander (1998) “All you need is RNA.” Science 281, 658-659.

Awards and Accomplishments

Robert P. and Debra Lee Faculty Fellowship 7/2008 – 8/2011
F. M. Kirby Family Faculty Fellowship, 7/2014 – 6/2017