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Published on: May 1, 2021
Mammalian mirtron genes
Eugene Berezikov1, Wei-Jen Chung, Jason Willis
1Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands. e.berezikov@niob.knaw.nl
Abstract:
Mirtrons are alternative precursors for microRNA biogenesis that were recently described in invertebrates. These short hairpin introns use splicing to bypass Drosha cleavage, which is otherwise essential for the generation of canonical animal microRNAs. Using computational and experimental strategies, we now establish that mammals have mirtrons as well. We identified 3 mirtrons that are well conserved and expressed in diverse mammals, 16 primate-specific mirtrons, and 46 candidates supported by limited cloning evidence in primates. As with some fly and worm mirtrons, the existence of well-conserved mammalian mirtrons indicates their relatively ancient incorporation into endogenous regulatory pathways. However, as worms, flies, and mammals each have different sets of mirtrons, we hypothesize that different animals may have independently evolved the capacity for this hybrid small RNA pathway. This notion is supported by our observation of several clade-specific features of mammalian and invertebrate mirtrons.
Insights
Mammals possess mirtrons, a novel microRNA precursor pathway bypassing Drosha cleavage. These findings suggest independent evolution of this hybrid small RNA pathway across different animal species.
Area of Science:
- Molecular Biology
- Genetics
- Bioinformatics
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression.
- Canonical miRNA biogenesis involves Drosha cleavage.
- Mirtrons, alternative miRNA precursors, were previously identified in invertebrates.
Purpose of the Study:
- To investigate the presence and characteristics of mirtrons in mammals.
- To determine the evolutionary origins and conservation of mirtrons.
Main Methods:
- Computational analysis of genomic data.
- Experimental validation including cloning and expression analysis.
- Comparative genomics across different species.
Main Results:
- Identification of 3 conserved mammalian mirtrons and numerous primate-specific mirtrons.
- Evidence of mirtrons in diverse mammalian species.
- Distinct sets of mirtrons observed in mammals, worms, and flies.
Conclusions:
- Mammals possess functional mirtrons, expanding the known miRNA biogenesis pathways.
- The independent evolution of mirtrons in different animal clades is supported.
- Mirtrons represent an ancient regulatory mechanism with clade-specific adaptations.
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