Regulatory Roles of Novel Small RNAs from Pseudogenes

Arising from gene duplications or retrotranspositions, pseudogenes are genomic sequences with high sequence similarity to functional genes but unable to encode the same type of functional molecular products as what their parental sequences produce. For those that are copies of protein-coding genes, this means that they have lost the potential of encoding a functional protein due to disruption in their putative open reading frames. Several computational algorithms have been developed for detecting pseudogenes in recent years and their applications have annotated hundreds and thousands of pseudogenes in higher eukaryotic genomes, including the rice and Arabidopsis genomes. While conventional wisdom considers pseudogenes as dead and inactive sequences, emerging evidence indicates that a large number of higher eukaryotic pseudogenes are transcriptionally alive and that furthermore many of the pseudogene transcripts may play a critical role in regulating gene expression. In particular, analyses of the RNAs from both plant and mammalian tissues or organs using deep-sequencing technology have uncovered scores of pseudogene-derived small RNAs. Their sequence features, together with carefully designed biochemical and genetic experiments, indicate that small RNAs from pseudogenes may function at different molecular levels, either as small interference RNAs directly regulating functional genes or modulating epigenomic silencing in the pseudogenic regions, or as decoy RNAs counteracting the inhibitory effectiveness of miRNAs supposedly targeting functional genes. These exciting discoveries suggest that pseudogenes may represent a hidden layer of regulatory elements in eukaryotic genomes, whose functional importance has just started to be unveiled and appreciated.