title: Human miRNA precursors with box H/ACA snoRNA features.
abstract: MicroRNAs (miRNAs) and small nucleolar RNAs (snoRNAs) are two classes of small non-coding regulatory RNAs, which have been much investigated in recent years. While their respective functions in the cell are distinct, they share interesting genomic similarities, and recent sequencing projects have identified processed forms of snoRNAs that resemble miRNAs. Here, we investigate a possible evolutionary relationship between miRNAs and box H/ACA snoRNAs. A comparison of the genomic locations of reported miRNAs and snoRNAs reveals an overlap of specific members of these classes. To test the hypothesis that some miRNAs might have evolved from snoRNA encoding genomic regions, reported miRNA-encoding regions were scanned for the presence of box H/ACA snoRNA features. Twenty miRNA precursors show significant similarity to H/ACA snoRNAs as predicted by snoGPS. These include molecules predicted to target known ribosomal RNA pseudouridylation sites in vivo for which no guide snoRNA has yet been reported. The predicted folded structures of these twenty H/ACA snoRNA-like miRNA precursors reveal molecules which resemble the structures of known box H/ACA snoRNAs. The genomic regions surrounding these predicted snoRNA-like miRNAs are often similar to regions around snoRNA retroposons, including the presence of transposable elements, target site duplications and poly (A) tails. We further show that the precursors of five H/ACA snoRNA-like miRNAs (miR-151, miR-605, mir-664, miR-215 and miR-140) bind to dyskerin, a specific protein component of functional box H/ACA small nucleolar ribonucleoprotein complexes suggesting that these molecules have retained some H/ACA snoRNA functionality. The detection of small RNA molecules that share features of miRNAs and snoRNAs suggest that these classes of RNA may have an evolutionary relationship.
authors.affiliation: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom. michelle@compbio.dundee.ac.uk
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Scott
authors.forename: Fabio
authors.initials: F
authors.lastname: Avolio
authors.forename: Motoharu
authors.initials: M
authors.lastname: Ono
authors.forename: Angus I
authors.initials: AI
authors.lastname: Lamond
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Barton
mesh_terms: D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D009690:Nucleic Acid Conformation; D012322:RNA Precursors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020537:RNA, Small Nucleolar / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C112148:DKC1 protein, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012322:RNA Precursors; D020537:RNA, Small Nucleolar