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Analysis of targeting mechanisms of tRNA derived fragments (tRFs)
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Karaiskos, Spyros. Analysis of targeting mechanisms of tRNA derived fragments (tRFs). Retrieved from https://doi.org/doi:10.7282/t3-59bk-d696

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TitleAnalysis of targeting mechanisms of tRNA derived fragments (tRFs)
NameKaraiskos, Spyros (author); Grigoriev, Andrey (chair); Klein, Eric (internal member); Nam, Jongmin (internal member); Ignatova, Zoya (outside member); Rutgers University; Camden Graduate School
Date Created2019
Other Date2019-01 (degree)
SubjectComputational and Integrative Biology, Transfer RNA
Extent1 online resource (141 pages : illustrations)
DescriptionWe characterized Drosophila melanogaster tRFs, which appear to have a number of structural and functional features similar to those of miRNAs. These tRFs show a number of similarities with miRNAs, including seed sequences. Based on complementarity with conserved Drosophila regions we identified such seed sequences and their possible targets with matches in the 3’ UTR regions. Strikingly, the potential target genes of the most abundant tRFs show significant Gene Ontology enrichment in development and neuronal function. The latter suggests that involvement of tRFs in the RNA interfering pathway may play a role in brain activity or brain changes with age.
Next, we observed different behavior of two types of tRNA fragments (3’ and 5’ tRFs) detected in significant numbers in rat brains. These fragments showed dynamic changes with age and 3’ tRFs were found to be increasing from young to mid-aged to old rats while 5’ tRFs displayed less consistent patterns. Further, 3’ tRFs showed a narrow range of sizes compared to 5’ tRFs suggesting different biogenesis mechanisms. Putative targets of these fragments were found to be enriched in neuronal and developmental functions.
Last, we describe interactions of human tRFs with their putative target RNAs associated with human Ago1 using Crosslinking, Ligation, And Sequencing of Hybrids (CLASH). We found that Argonaute-loaded tRFs target a wide range of transcripts corresponding to various gene types, in addition to protein-coding transcripts. In the latter, 3' UTR regions are the likely primary target of tRFs, although there is a significant number of interactions of tRFs with coding sequences and a small number of interactions between tRFs and 5' UTR regions. We also report a novel phenomenon – a large number of putative interactions between tRFs and intronic sequences. We analyzed sequences of chimeras formed in vivo between tRFs and their targets to identify clusters of RNA-RNA interaction signatures. We also identified enriched motifs that may be responsible for these interactions and we provide ample evidence supporting the notion that tRF “seed” sequences appear to be primarily located on the 5’ end of a tRF.
NotePh.D.
NoteIncludes bibliographical references
Noteby Spyros Karaiskos
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/t3-59bk-d696
Languageeng
CollectionCamden Graduate School Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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