In multicellular organisms a class of ~22nt small RNAs called microRNAs (miRNAs) controls the translation of a majority of protein-coding genes. This occurs through binding of short complementary sequences in mRNAs, which triggers their decay or destruction. Hundreds of miRNA genes are found in eukaryotic genomes that are produced through a variety of biogenesis pathways. Most miRNAs are processed by sequential cleavage of hairpin RNAs by the RNase III enzymes Drosha and Dicer. One alternative pathway involves short intron derived miRNAs, termed mirtrons, which eschew Drosha processing for splicing and lariat debranching. Some mirtrons possess additional ?tail? nucleotide residues, which require trimming by ribonucleases after splicing and debranching. Hundreds of these non-canonical miRNAs exist in the human genome, yet little is known regarding the function and biogenesis of these genes. The rapidly evolving nature of tailed-mirtrons complicates functional prediction using comparative genomic approaches. This combined with their relatively recent discovery, suggests the importance of tailed-mirtrons in human biology may be underestimated. To better understand this class of miRNA we will focus on Drosophila miR-1017, a relatively highly expressed tailed-mirtron that is deeply conserved across fly species. This miRNA will be used as a model for endogenous, efficiently processed tailed-mirtrons and represents a unique opportunity to study this class of genes.
We aim to identify the phenotypic contributions of miR-1017 and uncover additional sequence elements that contribute to its processing efficiency. We will also translate insight into tailed-mirtron biology gained from studying miR- 1017 to those found in mammalian genomes.
The advent of the genomic age in biology has brought about a gold rush for discovery of new genes. In particular there has been an explosion in number of genes described to only produce RNA molecules. The role of many newly discovered types of genes in biology however is unknown. This proposal seeks to determine if a group called tail mirtron has tangible in?uence on cell function.
| Mohammed, Jaaved; Flynt, Alex S; Panzarino, Alexandra M et al. (2018) Deep experimental profiling of microRNA diversity, deployment, and evolution across the Drosophila genus. Genome Res 28:52-65 |
| Zia, Mohammad Farid; Flynt, Alex S (2018) Detection and Verification of Mammalian Mirtrons by Northern Blotting. Methods Mol Biol 1823:209-219 |
