Agris Lab


AGRIS LABORATORY RESEARCHERS
PAUL F. AGRIS Professor of Biochemistry Curriculum Vitae For many years, Dr. Agris has been interested in, and has investigated the basic and applied aspects of RNA chemistry and structure. In particular, he is interested in how the posttranscriptional modifications of RNA alter chemistry and structure for the achievement of function, and how to use this knowledge in biomedicine. Most recently, his group has shown that modifications pre-structure the anticodon of tRNAs prior to their entry into the ribosome's A-site. The pre-structuring enables some tRNAs to read cognate and wobble codons, and restricts them to their two-fold degenerate codons. In contrast, the modification-dependent pre-structuring of other tRNAs enables them to read their cognate codons and to recognize the three remaining codons of their four-fold degenerate codes. Thus, the modifications expand the capability of these tRNAs to read all codons for their corresponding amino acids. He is now studying those tRNA involved in decoding six-fold degenerate codes. In collaboration with Dr. Venki Ramakrishnan, the Agris lab has described the structure of tRNA anticodons in the reading of two-fold and four-fold degenerate codons. With high resolution (2.5 Å) x-ray crystallography of the ribosomes 30S subunit, the anticodon/codon interaction can be clearly observed, thus revealing the position and effect of posttranslational modification at the wobble position and 3'-adjacent to the anticodon of tRNA. In other research, the group is studying the structure/function relationship of mitochondrial tRNAs, the control of gene expression by tRNA, the interaction of HIV with tRNA, and the interaction of aminoglycoside antibiotics with rRNA. Dr. Agris has pioneered a peptide selection technique to study the interactions of proteins with RNA, and modified RNAs, as well. HONORS ADVISOR TO THE POLISH ACADEMY OF SCIENCES ASSOCIATE EDITOR, RNA BIOLOGY VISITING SENIOR FELLOW, EXETER COLLEGE, OXFORD NATIONAL RESEARCH SERVICE AWARD SPECIAL FELLOW U.S. NATL. ACADEMY OF SCIENCE EXCHANGE SCIENTIST- POLISH ACADEMY OF SCIENCES PUBLICATIONS (RECENT) Weixlbaumer, A., Murphy, F.,Vendeix, F., Graham, W.D., Dziergowska, A., Gustilo, E., Sproat, B., Ramakrishnan, V., and Agris, P.F. (2007) The structure of four codon decoding by a modified uridine wobble base. Nature Struct. Mol. Biol., in press Eshete, M., Marchbank, M.T., Deutscher, S.L.,Smith, G.P. and Agris, P.F. (2007) Specificity of phage display selected peptides as tools for recognition of modified vs. unmodified anticodon stem and loop domains of tRNA. The Protein Journal, in press. Agris, P.F., Vendeix, F.A.P. and Graham, W.D. (2007) tRNA's Wobble Decoding of the Genome: 40 Years of Modification, J. Mol. Biol. 366, 1-13. Dressman, H.K., Barley-Maloney, L., Rowlette, L-L., Agris, P.F. and Garcia-Blanco, M.A. (2006) Assessing incomplete deprotection of microarray oligonucleosides in situ. Nucleic Acids Res. 34, e131. Barley-Maloney, L. and Agris, P.F. (2006) Quality assessment of commercial siRNA and DNA: monoclonal antibodies and a high through-put chemiluminescense assay. Analytical Biochemistry, 360,172-174. Nelson, A, Henkin, T. and Agris, P.F. (2006) Folding interactions of an mRNA 5’-UTR that regulates gene expression: Interaction with a regulatory tRNA. RNA 12, 1254-1261. Jones, C.I., Spencer, A.C., Hsu, J.L., Spremulli, L.L., Martinis, S.A. DeRider, M. and Agris, P.F. (2006) A counterintuitive Mg2+-dependent and modification-assisted functional folding of mitochondrial tRNAs. J. Mol. Biol., 362,771-786. Gagnon, G. Zhang, X., Agris, P.F. and Maxwell, S.E. (2006) Assembly of the Archaeal Box C/D sRNP Can Occur Via Alternative Pathways and Requires Temperature-Facilitated sRNA Remodeling, J. Mol. Biol., 362, 1025-1042. RESEARCH SUPPORT NATIONAL SCIENCE FOUNDATION AND NATIONAL INSTITUTES OF HEALTH; UNITED MITOCHONDRIAL DISEASE FOUNDATION KENAN INSTITUTE; VARIAN CORPORATION; DHARMACON RNA TECHNOLOGIES

AGRIS LABORATORY RESEARCHERS

PAUL F. AGRIS

Professor of Biochemistry
Curriculum Vitae

For many years, Dr. Agris has been interested in, and has investigated the basic and applied aspects of RNA chemistry and structure. In particular, he is interested in how the posttranscriptional modifications of RNA alter chemistry and structure for the achievement of function, and how to use this knowledge in biomedicine.
Most recently, his group has shown that modifications pre-structure the anticodon of tRNAs prior to their entry into the ribosome's A-site. The pre-structuring enables some tRNAs to read cognate and wobble codons, and restricts them to their two-fold degenerate codons. In contrast, the modification-dependent pre-structuring of other tRNAs enables them to read their cognate codons and to recognize the three remaining codons of their four-fold degenerate codes. Thus, the modifications expand the capability of these tRNAs to read all codons for their corresponding amino acids. He is now studying those tRNA involved in decoding six-fold degenerate codes.
In collaboration with Dr. Venki Ramakrishnan, the Agris lab has described the structure of tRNA anticodons in the reading of two-fold and four-fold degenerate codons. With high resolution (2.5 Å) x-ray crystallography of the ribosomes 30S subunit, the anticodon/codon interaction can be clearly observed, thus revealing the position and effect of posttranslational modification at the wobble position and 3'-adjacent to the anticodon of tRNA.
In other research, the group is studying the structure/function relationship of mitochondrial tRNAs, the control of gene expression by tRNA, the interaction of HIV with tRNA, and the interaction of aminoglycoside antibiotics with rRNA. Dr. Agris has pioneered a peptide selection technique to study the interactions of proteins with RNA, and modified RNAs, as well.

HONORS

ADVISOR TO THE POLISH ACADEMY OF SCIENCES
ASSOCIATE EDITOR, RNA BIOLOGY
VISITING SENIOR FELLOW, EXETER COLLEGE, OXFORD
NATIONAL RESEARCH SERVICE AWARD SPECIAL FELLOW
U.S. NATL. ACADEMY OF SCIENCE EXCHANGE SCIENTIST- POLISH ACADEMY OF SCIENCES

PUBLICATIONS (RECENT)

Weixlbaumer, A., Murphy, F.,Vendeix, F., Graham, W.D., Dziergowska, A., Gustilo, E., Sproat, B., Ramakrishnan, V., and Agris, P.F. (2007) The structure of four codon decoding by a modified uridine wobble base. Nature Struct. Mol. Biol., in press
Eshete, M., Marchbank, M.T., Deutscher, S.L.,Smith, G.P. and Agris, P.F. (2007) Specificity of phage display selected peptides as tools for recognition of modified vs. unmodified anticodon stem and loop domains of tRNA. The Protein Journal, in press.
Agris, P.F., Vendeix, F.A.P. and Graham, W.D. (2007) tRNA's Wobble Decoding of the Genome: 40 Years of Modification, J. Mol. Biol. 366, 1-13.
Dressman, H.K., Barley-Maloney, L., Rowlette, L-L., Agris, P.F. and Garcia-Blanco, M.A.
(2006) Assessing incomplete deprotection of microarray oligonucleosides in situ. Nucleic Acids Res. 34, e131.
Barley-Maloney, L. and Agris, P.F. (2006) Quality assessment of commercial siRNA and DNA: monoclonal antibodies and a high through-put chemiluminescense assay. Analytical Biochemistry, 360,172-174.
Nelson, A, Henkin, T. and Agris, P.F. (2006) Folding interactions of an mRNA 5’-UTR that regulates gene expression: Interaction with a regulatory tRNA. RNA 12, 1254-1261.
Jones, C.I., Spencer, A.C., Hsu, J.L., Spremulli, L.L., Martinis, S.A. DeRider, M. and Agris, P.F. (2006) A counterintuitive Mg2+-dependent and modification-assisted functional folding of mitochondrial tRNAs. J. Mol. Biol., 362,771-786.
Gagnon, G. Zhang, X., Agris, P.F. and Maxwell, S.E. (2006) Assembly of the Archaeal Box C/D sRNP Can Occur Via Alternative Pathways and Requires Temperature-Facilitated sRNA Remodeling, J. Mol. Biol., 362, 1025-1042.

RESEARCH SUPPORT

NATIONAL SCIENCE FOUNDATION AND NATIONAL INSTITUTES OF HEALTH;
UNITED MITOCHONDRIAL DISEASE FOUNDATION
KENAN INSTITUTE; VARIAN CORPORATION; DHARMACON RNA TECHNOLOGIES