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Faculty & Staff

Education

B.S. 1964 Iowa Wesleyan College
Ph.D. 1968 Purdue University
Postdoctoral Research: Medical Research Council, Laboratory of Molecular Biology Cambridge, England

Areas of Study

tRNA structure and function

Research Overview

William H. McClain is Halvorson Professor of Bacteriology and Molecular Biology, Emeritus, at the University of Wisconsin-Madison. His theoretical and bench experiments (1967-present) unravel the mechanisms of complex and essential biological processes and set him apart as a pioneer in the biological sciences.

RNA figure

TRANSFER RNA (tRNA) converts the instructions in a gene into amino acid subunits, forming protein. Proteins are composed of 20 amino acid types, wherein each amino acid type corresponds to one type of tRNA. The tRNA is built of nucleotide subunits. The sequence of nucleotides in a tRNA is highly variable and determines the specificity of each tRNA for its amino acid.

REPRESENTATION of a tRNA, comprised of a repeating backbone (blue line) with one of four pendent nucleotides at 76 sites (yellow circles). McClain's original computational analysis of the nucleotide sequences of the 20 types of tRNA enabled him to predict which nucleotides were both favored by each tRNA acceptor type and disfavored by the other 19 tRNAs. Larger yellow circles were more predictive. Guided by computer analysis, he chemically redesigned a tRNA gene from type #1 to type #2. Protein sequencing revealed that cells containing the redesigned tRNA switched their specificity to that of type #2.

Research Papers

  • McClain WH (2010) Discovery of a mini-RNase P in archaea. Proc. Natl. Acad. Sci. U.S.A. 107(52):22371-2 (PMC3012473) · Pubmed

    No abstract available.

  • McClain WH, Lai LB, Gopalan V (2010) Trials, travails and triumphs: an account of RNA catalysis in RNase P. J. Mol. Biol. 397(3):627-46 · Pubmed

    No abstract available.

  • McClain WH (2006) Surprising contribution to aminoacylation and translation of non-Watson-Crick pairs in tRNA. Proc. Natl. Acad. Sci. U.S.A. 103(12):4570-5 (PMC1450212) · Pubmed

    No abstract available.

  • McClain WH, Gabriel K, Lee D, Otten S (2004) Structure-function analysis of tRNA(Gln) in an Escherichia coli knockout strain. RNA 10(5):795-804 (PMC1370570) · Pubmed

    No abstract available.

  • Lee D, McClain WH (2004) Aptamer redesigned tRNA is nonfunctional and degraded in cells. RNA 10(1):7-11 (PMC1370512) · Pubmed

    No abstract available.

  • Choi H, Gabriel K, Schneider J, Otten S, McClain WH (2003) Recognition of acceptor-stem structure of tRNA(Asp) by Escherichia coli aspartyl-tRNA synthetase. RNA 9(4):386-93 (PMC1370406) · Pubmed

    No abstract available.

  • Choi H, Otten S, Schneider J, McClain WH (2002) Genetic perturbations of RNA reveal structure-based recognition in protein-RNA interaction. J. Mol. Biol. 324(4):573-6 · Pubmed

    No abstract available.

  • Choi H, Otten S, McClain WH (2002) Isolation of novel tRNA(Ala) mutants by library selection in a tRNA(Ala) knockout strain. Biochimie 84(8):705-11 · Pubmed

    No abstract available.

  • Moulinier L, Eiler S, Eriani G, Gangloff J, Thierry JC, Gabriel K, McClain WH, Moras D (2001) The structure of an AspRS-tRNA(Asp) complex reveals a tRNA-dependent control mechanism. EMBO J. 20(18):5290-301 (PMC125622) · Pubmed

    No abstract available.

  • Gabriel K, McClain WH (2001) Plasmid systems to study RNA function in Escherichia coli. J. Mol. Biol. 310(3):543-8 · Pubmed

    No abstract available.

  • McClain WH, Gabriel K (2001) Construction of an Escherichia coli knockout strain for functional analysis of tRNA(Asp). J. Mol. Biol. 310(3):537-42 · Pubmed

    No abstract available.

  • Varani G, McClain WH (2000) The G x U wobble base pair. A fundamental building block of RNA structure crucial to RNA function in diverse biological systems. EMBO Rep. 1(1):18-23 (PMC1083677) · Pubmed

    No abstract available.

  • Strazewski P, Biala E, Gabriel K, McClain WH (1999) The relationship of thermodynamic stability at a G x U recognition site to tRNA aminoacylation specificity. RNA 5(11):1490-4 (PMC1369870) · Pubmed

    No abstract available.

  • Chang KY, Varani G, Bhattacharya S, Choi H, McClain WH (1999) Correlation of deformability at a tRNA recognition site and aminoacylation specificity. Proc. Natl. Acad. Sci. U.S.A. 96(21):11764-9 (PMC18360) · Pubmed

    No abstract available.

  • McClain WH, Jou YY, Bhattacharya S, Gabriel K, Schneider J (1999) The reliability of in vivo structure-function analysis of tRNA aminoacylation. J. Mol. Biol. 290(2):391-409 · Pubmed

    No abstract available.

  • Gabriel K, McClain WH (1999) A set of plasmids constitutively producing different RNA levels in Escherichia coli. J. Mol. Biol. 290(2):385-9 · Pubmed

    No abstract available.

  • McClain WH, Gabriel K, Bhattacharya S, Jou YY, Schneider J (1999) Functional compensation by particular nucleotide substitutions of a critical G*U wobble base-pair during aminoacylation of transfer RNA. J. Mol. Biol. 286(4):1025-32 · Pubmed

    No abstract available.

  • Cermakian N, McClain WH, Cedergren R (1998) tRNA nucleotide 47: an evolutionary enigma. RNA 4(8):928-36 (PMC1369670) · Pubmed

    No abstract available.

  • McClain WH, Schneider J, Bhattacharya S, Gabriel K (1998) The importance of tRNA backbone-mediated interactions with synthetase for aminoacylation. Proc. Natl. Acad. Sci. U.S.A. 95(2):460-5 (PMC18442) · Pubmed

    No abstract available.

  • McClain WH, Gabriel K, Schneider J (1996) Specific function of a G.U wobble pair from an adjacent helical site in tRNA(Ala) during recognition by alanyl-tRNA synthetase. RNA 2(2):105-9 (PMC1369355) · Pubmed

    No abstract available.

  • Gabriel K, Schneider J, McClain WH (1996) Functional evidence for indirect recognition of G.U in tRNA(Ala) by alanyl-tRNA synthetase. Science 271(5246):195-7 · Pubmed

    No abstract available.

  • Nicholas HB, McClain WH (1995) Searching tRNA sequences for relatedness to aminoacyl-tRNA synthetase families. J. Mol. Evol. 40(5):482-6 · Pubmed

    No abstract available.

  • McClain WH, Schneider J, Gabriel K (1994) Association of tRNA(Gln) acceptor identity with phosphate-sugar backbone interactions observed in the crystal structure of the Escherichia coli glutaminyl-tRNA synthetase-tRNA(Gln) complex. Biochimie 75(12):1125-36 · Pubmed

    No abstract available.

  • McClain WH, Schneider J, Gabriel K (1994) Distinctive acceptor-end structure and other determinants of Escherichia coli tRNAPro identity. Nucleic Acids Res. 22(3):522-9 (PMC523613) · Pubmed

    No abstract available.

  • McClain WH (1993) Rules that govern tRNA identity in protein synthesis. J. Mol. Biol. 234(2):257-80 · Pubmed

    No abstract available.

  • McClain WH (1993) Identity of Escherichia coli tRNA(Cys) determined by nucleotides in three regions of tRNA tertiary structure. J. Biol. Chem. 268(26):19398-402 · Pubmed

    No abstract available.

  • McClain WH (1993) Transfer RNA identity. FASEB J. 7(1):72-8 · Pubmed

    No abstract available.

  • McClain WH, Foss K, Jenkins RA, Schneider J (1991) Four sites in the acceptor helix and one site in the variable pocket of tRNA(Ala) determine the molecule's acceptor identity. Proc. Natl. Acad. Sci. U.S.A. 88(20):9272-6 (PMC52696) · Pubmed

    No abstract available.

  • McClain WH, Foss K, Jenkins RA, Schneider J (1991) Rapid determination of nucleotides that define tRNA(Gly) acceptor identity. Proc. Natl. Acad. Sci. U.S.A. 88(14):6147-51 (PMC52039) · Pubmed

    No abstract available.

  • McClain WH, Foss K, Jenkins RA, Schneider J (1990) Nucleotides that determine Escherichia coli tRNA(Arg) and tRNA(Lys) acceptor identities revealed by analyses of mutant opal and amber suppressor tRNAs. Proc. Natl. Acad. Sci. U.S.A. 87(23):9260-4 (PMC55144) · Pubmed

    No abstract available.

  • McClain WH, Chen YM, Foss K, Schneider J (1988) Association of transfer RNA acceptor identity with a helical irregularity. Science 242(4886):1681-4 · Pubmed

    No abstract available.

  • McClain WH (1988) Specific duplications fostered by a DNA structure containing adjacent inverted repeat sequences. J. Mol. Biol. 204(1):27-40 · Pubmed

    No abstract available.

  • McClain WH, Wilson JH, Seidman JG (1988) Genetic analysis of structure and function in phage T4 tRNASer. J. Mol. Biol. 203(3):549-53 · Pubmed

    No abstract available.

  • McClain WH, Foss K (1988) Changing the acceptor identity of a transfer RNA by altering nucleotides in a "variable pocket". Science 241(4874):1804-7 · Pubmed

    No abstract available.

  • Lawrence N, Wesolowski D, Gold H, Bartkiewicz M, Guerrier-Takada C, McClain WH, Altman S (1988) Characteristics of ribonuclease P from various organisms. Cold Spring Harb. Symp. Quant. Biol. 52:233-8 · Pubmed

    No abstract available.

  • McClain WH, Foss K (1988) Nucleotides that contribute to the identity of Escherichia coli tRNA(Phe). J. Mol. Biol. 202(4):697-709 · Pubmed

    No abstract available.

  • McClain WH, Foss K (1988) Changing the identity of a tRNA by introducing a G-U wobble pair near the 3' acceptor end. Science 240(4853):793-6 · Pubmed

    No abstract available.

  • Foss K, McClain WH (1988) Rapid site-specific mutagenesis in plasmids. Gene 59(2-3):285-90 · Pubmed

    No abstract available.

  • McClain WH, Guerrier-Takada C, Altman S (1987) Model substrates for an RNA enzyme. Science 238(4826):527-30 · Pubmed

    No abstract available.

  • McClain WH, Seidman JG (1987) Genetic conversion of G.C base-pairs to A.U base-pairs in a transfer RNA. J. Mol. Biol. 197(3):605-8 · Pubmed

    No abstract available.

  • Nicholas HB, McClain WH (1987) An algorithm for discriminating sequences and its application to yeast transfer RNA. Comput. Appl. Biosci. 3(3):177-81 · Pubmed

    No abstract available.

  • McClain WH, Nicholas HB (1987) Differences between transfer RNA molecules. J. Mol. Biol. 194(4):635-42 · Pubmed

    No abstract available.

  • Nicholas HB, Chen YM, McClain WH (1987) Comparison of tRNA sequences. Comput. Appl. Biosci. 3(1):53 · Pubmed

    No abstract available.

  • McClain WH, Foss K, Schneider J, Guerrier-Takada C, Altman S (1987) Suppressor and novel mutants of bacteriophage T4 tRNA(Gly). J. Mol. Biol. 193(1):223-6 · Pubmed

    No abstract available.

  • McClain WH, Foss K, Mittelstadt KL, Schneider J (1986) Variants in clones of gene-machine-synthesized oligodeoxynucleotides. Nucleic Acids Res. 14(16):6770 (PMC311683) · Pubmed

    No abstract available.

  • Atilgan T, Nicholas HB, McClain WH (1986) A statistical method for correlating tRNA sequence with amino acid specificity. Nucleic Acids Res. 14(1):375-80 (PMC339420) · Pubmed

    No abstract available.

  • McClain WH, Foss K (1984) Hybrid transfer RNA genes in phage T4. Cell 38(1):225-31 · Pubmed

    No abstract available.

  • Guerrier-Takada C, McClain WH, Altman S (1984) Cleavage of tRNA precursors by the RNA subunit of E. coli ribonuclease P (M1 RNA) is influenced by 3'-proximal CCA in the substrates. Cell 38(1):219-24 · Pubmed

    No abstract available.