Title page for ETD etd-05262006-013154


Type of Document Dissertation
Author Cui, Zhengfang
Author's Email Address zcui1@lsu.edu
URN etd-05262006-013154
Title RNAi Knockdown of Nopp140 Induces the Minute Syndrome in Drosophila: A Potential Model for the Human Treacher Collins Syndrome
Degree Doctor of Philosophy (Ph.D.)
Department Biochemistry (Biological Sciences)
Advisory Committee
Advisor Name Title
Patrick J. DiMario Committee Chair
Craig M. Hart Committee Member
Ding S. Shih Committee Member
Sue G. Bartlett Committee Member
Kenneth E. Damann Dean's Representative
Keywords
  • nucleolus
  • rnai
  • minute syndrome
  • treacher collins
  • ribosome biogenesis
  • nopp140
Date of Defense 2006-05-01
Availability unrestricted
Abstract
Nopp140 is believed to play a chaperone function in pre-rRNA processing and ribosome assembly. Alternative splicing in Drosophila may yield two isoforms: the first, Nopp140-True, shares a conserved carboxy terminus with human Nopp140. The second contains a distinctive glycine and arginine rich (RGG) carboxy terminus typically found in vertebrate nucleolin. To further characterize Nopp140 in Drosophila, we expressed interfering RNAs in transgenic flies using the GAL4 inducible system. RT-PCR and Western blot analyses showed a loss of Nopp140 mRNA and protein in transgenic larvae. Resulting phenotypes fall within the Minute syndrome of Drosophila; they include slow growth, larval and pupal lethality, or variably deformed wings, legs, and tergites in surviving adults. Analogous to the Drosophila Minute syndrome is the human Treacher Collins syndrome which displays craniofacial birth defects due to the haplo-insufficiency in treacle, a nucleolar protein structurally related to Nopp140. We further show that severe over-expression of GFP-Nopp140-True or GFP-Nopp140-RGG in a GAL4-dependent manner is also embryonic and larval lethal. We could mutually complement RNAi-induced lethality and lethality caused by over-expression in trans-heterozygous flies. Expressing either of the two Nopp140 isoforms rescued RNAi-induced lethality, suggesting functional overlap between the two proteins.
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