title: Human intron-encoded AluACA RNAs and telomerase RNA share a common element promoting RNA accumulation.
abstract: Mammalian cells express hundreds of intron-encoded box H/ACA RNAs which fold into a common hairpin-hinge-hairpin-tail structure, interact with 4 evolutionarily conserved proteins, dyskerin, Nop10, Nhp2 and Gar1, and function mainly in RNA pseudouridylation. The human telomerase H/ACA RNA (hTR) directs telomeric DNA synthesis and it carries a 5'-terminal domain encompassing the telomeric template sequence. The primary hTR transcript is synthesized from an independent gene by RNA polymerase II and undergoes 3' end processing controlled by the 3'-terminal H/ACA domain. The apical stem-loop of the 3' hairpin of hTR carries a unique biogenesis-promoting element, the BIO motif that promotes hTR processing and RNP assembly. AluACA RNAs represent a distinct class of human H/ACA RNAs; they are processed from intronic Alu repetitive sequences. As compared to canonical H/ACA RNAs, the AluACA RNAs carry unusually short or long 5' hairpins and generally, they accumulate at low levels. Here, we demonstrate that the suboptimal 5' hairpins are responsible for the weak expression of AluACA RNAs. We also show that AluACA RNAs frequently carry a processing/stabilization element that is structurally and functionally indistinguishable from the hTR BIO motif. Both hTR and AluACA biogenesis-promoting elements are located in the terminal stem-loop of the 3'-terminal H/ACA hairpin, they show perfect structural conservation and are functionally interchangeable in in vivo RNA processing reactions. Our results demonstrate that the BIO motif, instead of being confined to hTR, is a more general H/ACA RNP biogenesis-facilitating element that can also promote processing/assembly of intron-encoded AluACA RNPs.
authors.affiliation: a Laboratoire de Biologie Moléculaire Eucaryote du CNRS, UMR5099, Center de Biologie Intégrative, Université Paul Sabatier , Toulouse Cedex 9, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Ketele
authors.affiliation: a Laboratoire de Biologie Moléculaire Eucaryote du CNRS, UMR5099, Center de Biologie Intégrative, Université Paul Sabatier , Toulouse Cedex 9, France.|b Biological Research Center, Hungarian Academy of Sciences , Szeged , Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Kiss
authors.affiliation: a Laboratoire de Biologie Moléculaire Eucaryote du CNRS, UMR5099, Center de Biologie Intégrative, Université Paul Sabatier , Toulouse Cedex 9, France.
authors.forename: Beáta E
authors.initials: BE
authors.lastname: Jády
mesh_terms: D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000378:metabolism*; D017393:RNA Editing; D012319:RNA Polymerase II / Q000378:metabolism*; D019098:Telomerase / Q000737:chemistry / Q000378:metabolism; D016615:Telomere / Q000235:genetics
chemical_list: C422952:telomerase RNA; D012313:RNA; D012319:RNA Polymerase II; D019098:Telomerase
keywords: AluACA RNAs; Box H/ACA RNAs; H/ACA RNA processing; H/ACA RNP biogenesis; intronic RNA processing; telomerase RNA