Skip to Main content Skip to Navigation
New interface
Journal articles

Guide RNA acrobatics: positioning consecutive uridines for pseudouridylation by H/ACA pseudouridylation loops with dual guide capacity

Abstract : Site-specific pseudouridylation of human ribosomal and spliceosomal RNAs is directed by H/ACA guide RNAs composed of two hairpins carrying internal pseudouridylation guide loops. The distal “antisense” sequences of the pseudouridylation loop base-pair with the target RNA to position two unpaired target nucleotides 5′-UN-3′, including the 5′ substrate U, under the base of the distal stem topping the guide loop. Therefore, each pseudouridylation loop is expected to direct synthesis of a single pseudouridine (Ψ) in the target sequence. However, in this study, genetic depletion and restoration and RNA mutational analyses demonstrate that at least four human H/ACA RNAs (SNORA53, SNORA57, SCARNA8, and SCARNA1) carry pseudouridylation loops supporting efficient and specific synthesis of two consecutive pseudouridines (ΨΨ or ΨNΨ) in the 28S (Ψ3747/Ψ3749), 18S (Ψ1045/Ψ1046), and U2 (Ψ43/Ψ44 and Ψ89/Ψ91) RNAs, respectively. In order to position two substrate Us for pseudouridylation, the dual guide loops form alternative base-pairing interactions with their target RNAs. This remarkable structural flexibility of dual pseudouridylation loops provides an unexpected versatility for RNA-directed pseudouridylation without compromising its efficiency and accuracy. Besides supporting synthesis of at least 6% of human ribosomal and spliceosomal Ψs, evidence indicates that dual pseudouridylation loops also participate in pseudouridylation of yeast and archaeal rRNAs.
Document type :
Journal articles
Complete list of metadata

https://hal-cnrs.archives-ouvertes.fr/hal-03806184
Contributor : Beata Jady Connect in order to contact the contributor
Submitted on : Monday, October 10, 2022 - 9:05:47 AM
Last modification on : Wednesday, November 23, 2022 - 11:58:26 AM

File

70.pdf
Publication funded by an institution

Identifiers

Collections

Citation

Beáta Jády, Amandine Ketele, Dylan Moulis, Tamás Kiss. Guide RNA acrobatics: positioning consecutive uridines for pseudouridylation by H/ACA pseudouridylation loops with dual guide capacity. Genes and Development, 2022, 36 (1-2), pp.70-83. ⟨10.1101/gad.349072.121⟩. ⟨hal-03806184⟩

Share

Metrics

Record views

0

Files downloads

0