(08-0327) Prof. Juli Feigon, UCLA

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  • Date/Time:
    • Thursday March 27, 2008
      3:00 pm - 4:00 pm
  • Location: G011 MS&E Bldg
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Contact
Shirley Tomes
Chemistry & Biochemistry
Contact Shirley Tomes
404-894-0591
Summaries

Summary Sentence: Prof. Juli Feigon, UCLA

Full Summary: Prof. Juli Feigon, University of California, Los Angeles Structural biology of telomerase and H/ACA RNA

Prof. Juli Feigon, University of California, Los Angeles

Structural biology of telomerase and H/ACA RNA

The telomere ends of linear chromosomes are replicated by the riboprotein complex telomerase. Telomerase uses an integral RNA template and a specialized reverse transcriptase to processively synthesize the G-rich strand. Telomerase has only a low or undetectable level of activity in normal somatic cells, but is highly active in most cancers, and is thus of interest as a target for anticancer drugs. In addition, mutations in the telomerase RNA have been found to cause some forms of the genetic diseases dyskeratosis congenita and aplastic anemia. Human telomerase is a large riboprotein complex that contains a 451 nt RNA along with a variety of proteins besides the telomerase reverse transcriptase. The RNA plays an integral role in catalysis, localization, and processing. Results on the structure of domains of the RNA component of telomerase, and how mutations in the RNA affect the structure and function of telomerase, will be presented.

During the biogenesis of eukaryotic ribosomal RNA (rRNA) and spliceosomal small nuclear RNA (snRNA), uridines at specific sites are converted to pseudouridines by H/ACA ribonucleoprotein particles (RNPs). Each H/ACA RNP contains a substrate-specific H/ACA RNA and four common proteins, the pseudouridine synthase Cbf5, Nop10, Gar1, and Nhp2. In eukaryotes, the H/ACA RNA contains two pseudouridylation (ψ) pockets, one or both of which are complementary to the sequences flanking the target uridine in the substrate rRNA or snRNA. However, some H/ACA RNPs, e.g. this domain in telomerase, do not appear to play a role in guiding pseudouridylation. Results on our structural studies of the H/ACA RNAs that guide rRNA modification as well as the H/ACA domain in telomerase will be presented.

Selected references:

C.A. Theimer, C.A. Blois, and J. Feigon: "Structure of the human telomerase RNA pseudoknot reveals conserved tertiary interactions essential for function", Mol. Cell 17, 671-682 (2005).

C.A. Theimer and J. Feigon: "Structure and function of telomerase RNA", Curr. Opin. Struct. Biol. 16, 307-318 (2006).

H. Wu and J. Feigon: "H/ACA small nucleolar RNA pseudouridylation pockets bind substrate RNA to form three-way junctions that position the target U for modification", Proc. Natl. Acad. Sci. USA 104, 6655-6660 (2007).

C.A. Theimer, B.E. Jady, N. Chim, P. Richard, K.E. Breece, T. Kiss, and J. Feigon: "Structural and functional characterization of human telomerase RNA processing and Cajal body localization signals", Molecular Cell 27, 869-881(2007).

For more information contact Dr. Nick Hud (404-385-1162).

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chemistry
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  • Created By: Shirley Tomes
  • Workflow Status: Published
  • Created On: Feb 28, 2007 - 8:00pm
  • Last Updated: Oct 7, 2016 - 9:57pm