Loading
Eukaryotic genome sequencing projects led to the astonishing discovery that the number of protein-coding genes shows a surprisingly moderate increase during evolution, although the genome size is rapidly growing in higher eukaryotes. This finding led to the recently emerging view that in addition to the protein-coding genes, the eukaryotic genomes contain another, thus far hidden layer of genetic information. Indeed, during that past decade it became apparent that the eukaryotic genome encodes a tremendous number of non-protein-coding or non-coding RNAs (ncRNAs) which function as regulatory RNAs in all aspects of gene expression and thereby, largely contribute to the biological complexity of eukaryotic organisms. Box H/ACA RNAs represent an abundant, evolutionarily conserved and functionally diverse group of ncRNAs. The H/ACA RNAs function in pseudouridylation of various classes of cellular RNAs, nucleolytic processing of rRNAs, synthesis of telomeric DNA and they serve as substrates for microRNA processing. All H/ACA RNAs associate with four H/ACA core ribonucleoproteins, dyskerin, Nhp2, Nop10 and Gar1, and they accumulate either in the nucleolus or in the nucleoplasmic Cajal bodies. The Cajal body-specific H/ACA RNAs also associate with Wdr79. In our laboratory, recent characterization of human Wdr79-associated RNAs identified more than 400 novel putative H/ACA RNAs. Besides several canonical H/ACA RNAs, we identified 348 novel human H/ACA RNAs which are encoded by genomic Alu repetitive elements located within introns of protein-coding genes. We have demonstrated that the newly discovered Alu-derived H/ACA RNAs, termed AluACA RNAs, are synthesized and processed from pre-mRNA intronic Alu sequences in an H and ACA box-dependent manner. The mature AluACA RNPs associate with the four H/ACA core proteins and Wdr79, but unexpectedly, they co-localize with spliceosomal small nuclear (sn)RNAs in the nucleoplasm. The Alu elements are the most abundant repetitive elements in the human genome with largely unknown function. Originated from the 7SL signal recognition particle RNA gene, Alu elements were propagated by retrotransposition in the genomes of primates. Thus, the newly discovered AluACA RNAs represent a novel, abundant, human- or maybe primate-specific subclass of H/ACA RNAs. Here, I propose a research program to dissect the biogenesis, subnuclear trafficking and the cellular function of this fascinating group of human ncRNPs.
<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=anr_________::bda70eaf4c36cc33e66d440f019e772b&type=result"></script>');
-->
</script>