Yi-Tao Yu, Ph.D.

See information for Patients. Viewing information for Researchers.

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?

Current Appointments

• Associate Professor - Department of Biochemistry and Biophysics (SMD)

Education
PhD Molecular Biology	Case Western Reserve Univ	1994
MS Neurobiology	China - Free-Standing Inst	1988
BS Chemistry	China - Free-Standing Inst	1982

Recent Journal Articles
Showing the 5 most recent journal articles. (31 available)
Xiao, M.; Yang, C.; Schattner, P.; Yu, Y. T.;. "Functionality and substrate specificity of human box H/ACA guide RNAs". Rna 15 (2009): 176-86.
Karijolich J; Yu YT. "Insight into the Protein Components of the Box H/ACA RNP." Current proteomics. 2008; 5(2):129-137.
Zhao, X.; Yu, Y. T.;. "Targeted pre-mRNA modification for gene silencing and regulation". Nat Methods (2007).
Karijolich, J.; Yu, Y.T.;. "Pre-mRNA splicing". Wiley Encyclopedia of Chemical Biology. (ed. TP Begley) (2007): (in press).
Zhao X; Yu YT. "Incorporation of 5-fluorouracil into U2 snRNA blocks pseudouridylation and pre-mRNA splicing in vivo." Nucleic acids research. 2007; 35(2):550-8. Epub 2006 Dec 14.