Computational prediction of RNA-based gene regulatory mechanisms in human and Tetrahymena

Abstract

The diversity and profound impact of gene regulation mediated by small RNAs (sRNAs) is just beginning to come into focus. RNA interference (RNAi) pathways have been shown to mediate processes such as genomic rearrangement in ciliates and developmental timing and tissue differentiation in plants and animals. Here we present a computational study into the function of two distinct classes of sRNAs. In the first section, we examine an uncharacterized class of sRNAs isolated from the ciliate Tetrahymena thermophila, present functional comparison to known classes of sRNAs in other organisms, and note a strong and specific relationship to a novel sequence motif. In the second section, we examine the evolutionary impact of microRNAs (miRNAs), which mediate potent post-transcriptional repression on their targets. We observe that miRNAs with tissue-specific expression exert remarkable evolutionary pressure, compelling many preferentially coexpressed genes to avoid accumulating target sites. We present tissue-specific patterns of such target depletion and note strong agreement with experimentally obtained miRNA expression patterns. Conversely, we report enrichment for targeting among genes with expression patterns spatially or temporally complementary to the miRNAs', suggesting a widespread role of tissue identity maintenance for miRNA-mediated regulation.