Abstract
A structural and functional classification of H/ACA and H/ACA-like motifs is obtained from the analysis of the H/ACA guide RNAs which have been identified previously in the genomes of Euryarchaea (Pyrococcus) and Crenarchaea (Pyrobaculum). A unified structure/function model is proposed based on the common structural determinants shared by H/ACA and H/ACA-like motifs in both Euryarchaea and Crenarchaea. Using a computational approach, structural and energetic rules for the guide:target RNA-RNA interactions are derived from structural and functional data on the H/ACA RNP particles. H/ACA(-like) motifs found in Pyrococcus are evaluated through the classification and their biological relevance is discussed. Extra-ribosomal targets found in both Pyrococcus and Pyrobaculum might support the hypothesis of a gene regulation mediated by H/ACA(-like) guide RNAs in archaea.
Highlights
The H/ACA guide RNAs are part of a RNP machinery including several proteins (L7Ae, Cbf5, Nop10 and Gar1) which catalyzes the uridine-to-pseudouridine isomerization
The lower stem generally includes 9 base-pairs in the canonical H/ACA motifs and the distance between the ACA box and the base-pair closing the internal loop in the upper stem is around 15 nt; in the numerous H/ACA motifs present in P. abyssi, an empirical constraint between 14 and 15 nt was proposed [5]
The 2D folds proposed for the “productive” H/ACA guide RNAs involve a distance of 9 base-pairs [1, 16, 55] or 10 base-pairs [1, 16]
Summary
The H/ACA guide RNAs are part of a RNP machinery including several proteins (L7Ae, Cbf, Nop and Gar1) which catalyzes the uridine-to-pseudouridine isomerization. Extensive structural and functional studies have focused on the H/ACA RNAs and RNPs from P. abyssi [16, 17, 4, 18, 19, 5, 20, 21] and P. furiosus [3, 22, 23, 24, 25, 26, 5, 27, 28, 29] These studies describe the structure/function relationships for this RNA guide machinery associated with the RNA fold, the RNA:RNA interactions between the guide and its target(s) and the RNA:protein contacts (between L7Ae and the K-turn or K-loop motif, between Cbf and the ACA box, etc.). The discovery of ’atypical’ H/ACA motifs in the Pyrobaculum genus has suggested an alternate way for this machinery to assemble and achieve its function [30] These non-canonical H/ACA motifs, further designated as H/ACA-like motifs, are detected in this genus of Crenarchaea and differ from the canonical H/ACA motifs in that the lower stem is truncated. The structural and functional relevance of the H/ACA-like motifs proposed recently in P. abyssi [33] is evaluated according to the classfication
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