title: Deep sequencing of small RNAs identifies canonical and non-canonical miRNA and endogenous siRNAs in mammalian somatic tissues.
abstract: MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression. They are characterized by specific maturation processes defined by canonical and non-canonical biogenic pathways. Analysis of ∼0.5 billion sequences from mouse data sets derived from different tissues, developmental stages and cell types, partly characterized by either ablation or mutation of the main proteins belonging to miRNA processor complexes, reveals 66 high-confidence new genomic loci coding for miRNAs that could be processed in a canonical or non-canonical manner. A proportion of the newly discovered miRNAs comprises mirtrons, for which we define a new sub-class. Notably, some of these newly discovered miRNAs are generated from untranslated and open reading frames of coding genes, and we experimentally validate these. We also show that many annotated miRNAs do not present miRNA-like features, as they are neither processed by known processing complexes nor loaded on AGO2; this indicates that the current miRNA miRBase database list should be refined and re-defined. Accordingly, a group of them map on ribosomal RNA molecules, whereas others cannot undergo genuine miRNA biogenesis. Notably, a group of annotated miRNAs are Dgcr8 independent and DICER dependent endogenous small interfering RNAs that derive from a unique hairpin formed from a short interspersed nuclear element.
authors: Division of Oncology, Department of Surgery and Cancer, Imperial Centre for Translational and Experimental Medicine (ICTEM), Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK. l.castellano@imperial.ac.uk
authors: Leandro
authors: L
authors: Castellano
authors: Justin
authors: J
authors: Stebbing
mesh_terms: D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D017124:Conserved Sequence; D053487:DEAD-box RNA Helicases / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism; D015870:Gene Expression; D057809:HEK293 Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009690:Nucleic Acid Conformation; D009928:Organ Specificity; D011506:Proteins / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins; D043244:Ribonuclease III / Q000235:genetics; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: C474044:Dgcr8 protein, mouse; D035683:MicroRNAs; D011506:Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases