Description
TitleTemporal patterns of short non-coding RNA modifications and expression
Date Created2015
Other Date2015-05 (degree)
Extent1 online resource (x, 181 p. : ill.)
DescriptionWe investigated the function and properties of small RNAs, particularly microRNAs and tRNA-derived fragments (tRFs) with age. We report the characterization of a novel 3'-to- 5' exonuclease, Nibbler (Nbr), that generates differing isoforms of miRNAs in Drosophila.. We developed a robust approach to help identify and characterize 3' heterogeneity in microRNAs controlled by Nbr, which assisted in identifying age- associated traits, including neurodegeneration and lifespan. Subsequently, given the fact Nbr interacts with Ago1 and not Ago2, we observed an accumulation of certain isoforms, which lead us to ask if there were particular patterns and trends that were Ago-specific. Interestingly, we report a novel age-associated change of select isoforms with age that is Ago2 specific. RNA deep-sequencing analysis coupled with experimental evidence reflected an increased loading of miRNA isoforms into Ago2 with age. Essentially, the loss of methylated miRNAs led to accelerated brain degeneration and shortened lifespan. Intriguingly, we also observed and identified Ago-loaded tRFs, which appear to have properties similar to those of miRNAs. We found this class of small RNAs to also display age-associated changes. For the first time, we found that differentially loaded Drosophila tRFs mapping to both nuclear and mitochondrial tRNA genes associating with all 20 amino acids. These tRFs show a number of similarities with miRNAs, including seed sequences, suggesting a similar role and function. Moreover, we further characterized and predicted targets for these tRFs and show a significant enrichment in development and neuronal function, suggesting a role in brain-related processes with age. In sum, we discovered a novel component of the canonical microRNA biogenesis pathway, responsible for the generation of multiple isoforms. We also connected specific age- associated patterns and trends of select microRNA isoforms, which were found to impact proper brain development and lifespan. Moreover, we identified differentially loaded tRFs and elucidated their structures, loading, and expression patterns, which corresponded closely with microRNAs. Finally, we were able to identify tRF seed regions that potentially play a role in brain activity or brain changes with age.
NotePh.D.
NoteIncludes bibliographical references
Noteby Ammar S. Naqvi
Genretheses, ETD doctoral
Languageeng
CollectionCamden Graduate School Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
Statistical Profile