Validation of the Regulatory Potential of Tailed Mirtrons

University Of Southern Mississippi, Hattiesburg MS

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Abstract

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.