Mammalian Small Nucleolar RNAs Are Mobile Genetic Elements

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Abstract
Small nucleolar RNAs (snoRNAs) of the H/ACA box and C/D box categories guide the pseudouridylation and the 2′-O-ribose methylation of ribosomal RNAs by forming short duplexes with their target. Similarly, small Cajal body–specific RNAs (scaRNAs) guide modifications of spliceosomal RNAs. The vast majority of vertebrate sno/scaRNAs are located in introns of genes transcribed by RNA polymerase II and processed by exonucleolytic trimming after splicing. A bioinformatic search for orthologues of human sno/scaRNAs in sequenced mammalian genomes reveals the presence of species- or lineage-specific sno/scaRNA retroposons (sno/scaRTs) characterized by an A-rich tail and an ∼14-bp target site duplication that corresponds to their insertion site, as determined by interspecific genomic alignments. Three classes of snoRTs are defined based on the extent of intron and exon sequences from the snoRNA parental host gene they contain. SnoRTs frequently insert in gene introns in the sense orientation at genomic hot spots shared with other genetic mobile elements. Previously characterized human snoRNAs are encoded in retroposons whose parental copies can be identified by phylogenic analysis, showing that snoRTs can be faithfully processed. These results identify snoRNAs as a new family of mobile genetic elements. The insertion of new snoRNA copies might constitute a safeguard mechanism by which the biological activity of snoRNAs is maintained in spite of the risk of mutations in the parental copy. I furthermore propose that retroposition followed by genetic drift is a mechanism that increased snoRNA diversity during vertebrate evolution to eventually acquire new RNA-modification functions. Large parts of vertebrate genomes are made of repeated sequences that were first considered to be junk DNA, but are now recognized as important actors in genome evolution. Most are genetic mobile elements that can gain additional genomic copies by a copy-and-paste mechanism involving an RNA intermediate. One class, the L1 elements, encodes two proteins required for its integration at new sites. Others, like primate Alu elements, hijack the L1 machinery for their mobilization, and are thus referred to as nonautonomous. In this article, Weber describes a new class of vertebrate nonautonomous mobile elements derived from small nucleolar RNAs (snoRNAs). These nonprotein-coding RNAs are encoded in gene introns and are involved in chemical modifications of selected bases of ribosomal RNAs. The article shows that new snoRNA copies were generated in vertebrate genomes via the copy-and-paste mechanism. Many of them are species-specific, and their insertion point was precisely determined by alignment with the corresponding genomic portion from a neighbour species. The mobilization of snoRNA gene sequences might ensure the presence of a functional copy when the parental one becomes invalidated by mutations. Moreover, such copies could evolve on their own to acquire the capacity of guiding new modifications of ribosomal RNAs.