The regulation of human Dicer.
Published: 2004
Language: eng
Number of pages: 132
Description: The Dicer enzyme is a key component of the RNA interference (RNAi) pathway and also responsible for the processing of microRNAs (miRNAs). Little is known about the structure and regulation of human Dicer mRNA. A comprehensive characterization of Dicer 5'-untranslated region (5'-UTR) RNA structure revealed important diversity within human Dicer mRNA transcripts. Three exon 1 variants were defined, some of which exhibited restricted patterns of tissue distribution. Three alternatively spliced 5'-leader exons were also noted. Surprisingly, this diversity all occurred within the 5'-UTR of Dicer mRNAs. The 5'-UTR variants had profound effects on translational efficiency. Considering the antiviral role of RNAi in other species, additional studies were conducted to understand whether cytokines alter Dicer expression. Primary human endothelial cells treated with interferon-beta or TNF-alpha demonstrated reduced steady-state levels of Dicer mRNA. These findings suggest potential interaction of proinflammatory stimuli with Dicer and the pathways in which it is involved.
Notes: Adviser:  Philip A. Marsden.

Thesis (M.Sc.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Masters Abstracts International, Volume: 43-03, page: 0787.

MICR copy on microfiche (2 microfiches).