Date of Award
Fall 10-11-2021
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
School
Biological, Environmental, and Earth Sciences
Committee Chair
Alex S. Flynt
Committee Chair School
Biological, Environmental, and Earth Sciences
Committee Member 2
Mohamed Elasri
Committee Member 2 School
Biological, Environmental, and Earth Sciences
Committee Member 3
YanLin Guo
Committee Member 3 School
Biological, Environmental, and Earth Sciences
Committee Member 4
Has Xu
Committee Member 4 School
Biological, Environmental, and Earth Sciences
Committee Member 5
Fengwei Bai
Committee Member 5 School
Biological, Environmental, and Earth Sciences
Abstract
Approximately a thousand microRNAs (miRNAs) are documented from human cells. A third appear to transit non-canonical pathways that typically bypass processing by Drosha, the dedicated nuclear miRNA producing enzyme. The largest class of non-canonical miRNAs are mirtrons which eschew Drosha to mature through spliceosome activity. While mirtrons are found in several configurations, the vast majority of human mirtron species are 5’-tailed. For these mirtrons, a 3’ splice site defines the 3’ end of their hairpin precursor while a “tail” of variable length separates the 5’ base of the hairpin from the nearest splice site. How this tail is removed is not understood. Here we examine sequence motifs in 5’-tailed mirtrons and interactions with RNA turnover processes to characterize biogenesis processes. Through studying the high confidence 5’-tailed mirtron, hsa-miR-5010, we identify RNaseP as necessary and sufficient for “severing” the 5’ tail of this mirtron. Further, depletion of RNaseP activity globally decreased 5’-tailed mirtron expression implicating this endoribonuclease in biogenesis of the entire class. Moreover, as 5’-tailed mirtron biogenesis appears to be connected to tRNA processing we found a strong correlation between accumulation of tRNA fragments (tRFs) and 5’-tailed mirtron abundance. This suggests that dysregulation of tRNA processing seem in cancers also impact expression of the ~400 5’-tailed mirtrons encoded in the human genome.
ORCID ID
https://orcid.org/0000-0002-2513-9565
Copyright
Zia, 2021
Recommended Citation
Zia, Mohammad Farid, "Human 5’-tailed Mirtrons are Processed by RNaseP" (2021). Dissertations. 1962.
https://aquila.usm.edu/dissertations/1962
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