Adding gears to the RNA machine: discovery and characterisation of new classes of small RNAs in eukaryotes

Taft, Ryan (2009). Adding gears to the RNA machine: discovery and characterisation of new classes of small RNAs in eukaryotes PhD Thesis, Institute for Molecular Bioscience, The University of Queensland.

       
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Author Taft, Ryan
Thesis Title Adding gears to the RNA machine: discovery and characterisation of new classes of small RNAs in eukaryotes
School, Centre or Institute Institute for Molecular Bioscience
Institution The University of Queensland
Publication date 2009-08
Thesis type PhD Thesis
Supervisor Professor John S. Mattick
Total pages 289
Total colour pages 103
Total black and white pages 186
Subjects 06 Biological Sciences
Abstract/Summary Genome sequencing has yielded unparalleled insights into fundamental biological processes and the genetics that guide them. In contrast to expectations that protein-coding genes would be the primary output of eukaryotic genomes, however, it is now clear that the vast majority of transcription is devoted to noncoding RNAs (ncRNAs). Although originally regarded as 'transcriptional noise', it is now clear that these transcripts are essential regulators of genetic activity. In this thesis I build upon the hypothesis that the genomes of eukaryotes encode a regulatory 'RNA machine' dominated by ncRNAs. In the Introduction (Chapter 1) I discuss how prior gene models may have inadvertently prevented a full understanding of ncRNAs, review the transcriptional landscape of eukaryotes, and examine the biogenesis and function of small regulatory RNAs. In support of a role for ncRNAs in complex metazoa, Chapter 2 presents data showing a positive correlation between the proportion of non-protein-coding DNA and biological complexity, suggesting that the evolutionary trajectory of intricate developmental phenotypes may have been facilitated by ncRNAs. In the following chapters two more 'gears' are added to the RNA machine. Chapter 3 details the discovery of snoRNA-derived RNAs - an evolutionarily ancient class of Argonaute-assocaited RNA whose biogenesis overlaps with microRNAs (miRNAs) and silencing RNAs (siRNAs). Likewise, Chapter 4 reports a new class of ~18 nt transcription initiation RNAs (tiRNAs) derived from regions proximal to transcription start sites. tiRNAs are enriched at GC-rich promoters and regions of active transcription, implicating them in transcriptional regulation. Chapter 5 presents evidence that tiRNAs are restricted to metazoa, and describes a model of RNA Polymerase II dependent tiRNA biogenesis. This thesis concludes with a general discussion of the implications of these findings, and the potential development of RNA therapeutics. Gathering evidence suggests that eukaryotic genomes are driven by a complex and interwoven network of RNA regulatory feedback loops. This thesis takes a small step towards developing a complete picture of this system.
Keyword genome
noncoding DNA
noncoding RNA
microRNA
piRNA
silencing RNA
transcript initiation RNA
small nucleolar RNA
sno-derived RNA
evolution
Additional Notes Color pages: 1,3-9,11,13-19,23,26-27,31-36,40-42,52-53,56-60,62,65,67,73,75,81,84-87,91,100-101,103-113,115-121,123,126-127,129-131,135-137,157,160,162-163,167,173,205,230,240-248,253,263,267,271,274-279,283 Landscape pages: 94-97, 152-154

 
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