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Associate Professor of Biochemistry and Biophysics
Ph.D. Case Western Reserve University 1994
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RNA modification, pre-mRNA splicing, snRNP biogenesis
Our long-range goal is to elucidate the underlying biological principles and functional roles of the posttranscriptional modifications of the small nuclear RNAs (snRNAs) involved in pre-mRNA splicing.The major spliceosomal snRNAs U1, U2, U4, U5, and U6 are present in eukaryotic cells as small nuclear ribonucleoprotein particles (snRNPs) that are essential for the splicing of the major class of introns. Notably, these snRNAs share common features of post-transcriptional modification. Aside from trimethylation of the 5’ guanosine cap (the exception is U6 that possesses a g-methyl guanosine cap), numerous internal nucleotides are also modified by pseudouridylation, 2´-O-methylation and, in some cases, base methylation. Importantly, the modified nucleotides in spliceosomal snRNAs are remarkably conserved from species to species, strongly suggesting that they are biologically significant. Yet, detailed investigation of this process has not been possible, due at least in part to the lack of effective assays and experimental systems. Recently, our lab and others developed several highly sensitive assays for detecting modified nucleotides in RNA. Using Xenopus oocytes, we also developed a powerful experimental system for performing extremely efficient modifications in spliceosomal snRNAs. For the first time, these newly developed assays, coupled with a Xenopus oocyte experimental system, provide us with tools to address the fundamental questions regarding spliceosomal snRNA modification. Using combined approaches of molecular biology and cell biology, we are currently focusing on three important areas of spliceosomal snRNA modification: (1)Which modified nucleotides are required for spliceosomal snRNA function and how do these modifications contribute to function? (2) Where do spliceosomal snRNA modifications occur within the cell? (3) What cellular machinery facilitates the modification of spliceosomal snRNAs, and what biochemical mechanisms are involved?
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Karijolich J, Yu YT (2007) Pre-mRNA splicing. Wiley Encyclopedia of Chemical Biology. (ed. TP Begley), (in press)
Zhao X, Yu YT (2007) Targeted pre-mRNA modification for gene silencing and regulation. Nat Methods,
Zhao X, Yu YT (2007) Incorporation of 5-fluorouracil into U2 snRNA blocks pseudouridylation and pre-mRNA splicing in vivo. Nucleic Acids Res, 35:550-8
Karijolich J, Stephenson D, Yu YT (2007) Biochemical purification of box H/ACA RNPs involved in pseudouridylation. Methods Enzymol, 425:241-62
Dai Q, Fong R, Saikia M, Stephenson D, Yu YT, Pan T, Piccirilli JA (2007) Identification of recognition residues for ligation-based detection and quantitation of pseudouridine and N6-methyladenosine. Nucleic Acids Res, 35:6322-9
Yu YT (2006) The most complex pseudouridylase. Structure, 14:167-8
Moon KH, Zhao X, Yu YT (2006) Pre-mRNA splicing in the nuclei of Xenopus oocytes. Methods Mol Biol, 322:149-63
Ma X, Yang C, Alexandrov A, Grayhack EJ, Behm-Ansmant I, Yu YT (2005) Pseudouridylation of yeast U2 snRNA is catalyzed by either an RNA-guided or RNA-independent mechanism. Embo J, 24:2403-13
Yang C, McPheeters DS, Yu YT (2005) Psi35 in the branch site recognition region of U2 small nuclear RNA is important for pre-mRNA splicing in Saccharomyces cerevisiae. J Biol Chem, 280:6655-62
Yu Y-T, Terns RM, Terns MP (2005) Mechanisms and functions of RNA-guided RNA modifications. In Fine-tuning of RNA functions by modification and editing, Topics in Current Genetics series, vol. 12 (ed. H. Grosjean). Springer-Verlag Press, New York, USA, 223-262
Zhao X, Yu YT (2004) Detection and quantitation of RNA base modifications. Rna, 10:996-1002
Zhao X, Yu YT (2004) Pseudouridines in and near the branch site recognition region of U2 snRNA are required for snRNP biogenesis and pre-mRNA splicing in Xenopus oocytes. Rna, 10:681-90
Behm-Ansmant I, Urban A, Ma X, Yu YT, Motorin Y, Branlant C (2003) The Saccharomyces cerevisiae U2 snRNA:pseudouridine-synthase Pus7p is a novel multisite-multisubstrate RNA:Psi-synthase also acting on tRNAs. Rna, 9:1371-82
Ma X, Zhao X, Yu YT (2003) Pseudouridylation (Psi) of U2 snRNA in S. cerevisiae is catalyzed by an RNA-independent mechanism. Embo J, 22:1889-97
Zhao X, Li ZH, Terns RM, Terns MP, Yu YT (2002) An H/ACA guide RNA directs U2 pseudouridylation at two different sites in the branchpoint recognition region in Xenopus oocytes. Rna, 8:1515-25
Yu YT, Shu MD, Narayanan A, Terns RM, Terns MP, Steitz JA (2001) Internal modification of U2 small nuclear (sn)RNA occurs in nucleoli of Xenopus oocytes. J Cell Biol, 152:1279-88
Yu YT (2000) Site-specific 4-thiouridine incorporation into RNA molecules. Methods Enzymol, 318:71-88
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Graduate students in my laboratory work toward a Ph.D. degree in the following program[s]:
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Ph.D. in Biochemistry
Ph.D. in Genetics
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Ph.D. candidates in my laboratory may also be affiliated with these programs:
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click here to learn more and to apply to graduate school |
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E-Mail: YiTao_Yu@urmc.rochester.edu
Yitao Yu
Department of Biochemistry and Biophysics
University of Rochester School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, New York 14642
Office: Medical Center 3-6818
Telephone: (585) 275-1271; Fax: (585) 275-6007
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