De Novo Identification of Viral-Encoded MicroRNAs

Abstract: MicroRNAs (miRNAs) constitute an ubiquitous class of small non-protein-coding RNAs (ncRNAs) regulating gene expression in diverse biological processes during developmental timing, signal transduction, apoptosis, cell proliferation, and tumorigenesis across plants, animals, and even viruses [1,2]. Together with RNA-Induced Silencing Complex (RISC), hybridization between the mature miRNAs (typically about 22 nucleotides long ncRNAs) and the 3 ' untranslated regions of its targets mRNAs post-transcriptionally down-regulate potentially a multitude of target genes. Recently reported in human and animals, host miRNAs can constitutively inhibit [3] or promote [4] viral replication. In parallels, viruses have devised counter-defensive strategies using virus-encoded RNAi suppressors [5] and/or virus-encoded miRNAs [6,7] to alter the cellular miRNA milieu in ways beneficial for their viral replication. The detailed mechanism of viral miRNAs involved in disabling/hijacking the host defense is still largely unknown. The endeavor towards elucidating the complex viral/human miRNAs-target interactions is technically challenging as high-throughput experimental methods for identifying viral miRNAs and human mRNA targets are yet available. To date there are few experimentally validated viral miRNAs and even fewer viral/human miRNAs-target interactions, there remain many unanswered questions about the mechanism and degree of down-regulation