The fate of edited RNA in caenorhabditis elegans

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Publication Type dissertation
School or College School of Medicine
Department Biochemistry
Author Hellwig, Sabine
Title The fate of edited RNA in caenorhabditis elegans
Date 2007-08
Description In contrast to DNA, which functions to store genetic information, RNA effectuates genetic information. The versatility of RNA is evident in the multiple cellular functions RNA fulfills. RNA molecules are structural elements, catalysts, adaptors, messengers and regulators. Accordingly, RNA shows great diversity in nucleotide composition and structure. This dissertation explores how sequence and structural features of RNA influence the fate of RNA in nematode cells and impact the entire organism. First, the C. elegans noncoding transcript rncs-1 is characterized. Throughout development, rncs-1 is expressed in intestine and hypodermis. Upon starvation, transcription of rncs-1 is upregulated by an ELT-2-dependent mechanism. A feature of the rncs-1 transcript is its extended double-stranded structure. Double-stranded RNA is a substrate for the RNase III enzyme Dicer, which cleaves long RNA duplexes into ~23-nucleotide products that subsequently silence cognate messages. Surprisingly, rncs-1 RNA is resistant to Dicer cleavage in vitro, and additional studies demonstrate that secondary structural elements in rncs-1 occlude access of Dicer to the double-stranded region. While not a cleavage substrate for Dicer in vitro, rncs-1 inhibits Dicer activity. Significantly, overexpression of rncs-1 modulates expression of endogenous Dicer silencing targets in vivo. This result represents a previously uncharacterized cellular function of noncoding RNAs. Second, the effect of RNA editing on the subcellular localization of RNA is examined. Deamination of adenosine to inosine within double-stranded RNA is catalyzed by adenosine deaminases that act on RNA (ADARs). The majority of cellular inosine is found in noncoding sequences, but the function of inosine in noncoding regions of RNA is unknown. In contradiction to existing models for nuclear retention of ADAR-edited RNA, research presented here confirms that endogenous editing substrates of C. elegans are exported to the cytoplasm. Finally, in continuation of previous behavioral studies that revealed chemotaxis defects of C. elegans ADAR-mutants, the response of editing-deficient worms to dauer-inducing pheromone is assayed. Dauer pheromone controls the entry of C. elegans into a specialized, highly resistant alternative larval stage called dauer. Nematodes lacking ADARs are found to show wildtype dauer formation, indicating that ADAR activity is dispensable for response to dauer pheromone.
Type Text
Publisher University of Utah
Subject ADAR-mutants; Genomic DNA
Subject MESH RNA Editing; Genetics; Caenorhabditis elegans
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "The fate of edited RNA in caenorhabditis elegans." Spencer S. Eccles Health Sciences Library. Print version of "The fate of edited RNA in caenorhabditis elegans." available at J. Willard Marriott Library Special Collection. QL3.5 2007 .H44
Rights Management © Sabine Hellwig.
Format Medium application/pdf
Format Extent 2,382,108 bytes
Identifier undthes,5473
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Master File Extent 2,382,154 bytes
ARK ark:/87278/s6rx9dzk
Setname ir_etd
Date Created 2012-04-24
Date Modified 2012-04-24
ID 191731
Reference URL https://collections.lib.utah.edu/ark:/87278/s6rx9dzk