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.
Highlights
Small nucleolar RNAs and microRNAs are two classes of abundant non-coding regulatory RNAs that carry out fundamental cellular activities but that have only been comprehensively investigated in recent years
The major functions known for RNA were long believed to be either messenger RNAs, which function as intermediates between genes and proteins, or ribosomal RNAs and transfer RNAs which carry out the translation process
Newly discovered classes of small RNAs have been shown to play important cellular roles. These include microRNAs, which can regulate the production of specific proteins, and small nucleolar RNAs, which recognise and chemically modify specific sequences in ribosomal RNA
Summary
Small nucleolar RNAs (snoRNAs) and microRNAs (miRNAs) are two classes of abundant non-coding regulatory RNAs that carry out fundamental cellular activities but that have only been comprehensively investigated in recent years. SnoRNAs are small RNA molecules of approximately 60–300 nucleotides in length which generally serve as guides for the catalytic modification of selected ribosomal RNA nucleotides [1,2]. SnoRNAs associate with specific proteins, which are conserved amongst all eukaryotes, to form small nucleolar ribonucleoparticles (snoRNPs). The box C/D snoRNAs, which bind the four conserved core box C/D snoRNP proteins fibrillarin, NOP56, NOP5/NOP58 and NHP2L1, are involved in 29-O-ribose methylation. The box H/ACA snoRNAs, which bind the four conserved core box H/ACA snoRNP proteins DKC1 (dyskerin), GAR1, NHP2 and NOP10, catalyse pseudouridylation. Two box C/D snoRNAs have recently been found to be transcribed from independent RNA pol II units [4]
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