Structure of an internal loop motif with three consecutive Uâ¢U mismatches from stem-loop 1 in the 3'-UTR of the SARS-CoV-2 genomic RNA.
Nucleic Acids Res
; 52(11): 6687-6706, 2024 Jun 24.
Article
em En
| MEDLINE
| ID: mdl-38783391
ABSTRACT
The single-stranded RNA genome of SARS-CoV-2 is highly structured. Numerous helical stem-loop structures interrupted by mismatch motifs are present in the functionally important 5'- and 3'-UTRs. These mismatches modulate local helical geometries and feature unusual arrays of hydrogen bonding donor and acceptor groups. However, their conformational and dynamical properties cannot be directly inferred from chemical probing and are difficult to predict theoretically. A mismatch motif (SL1-motif) consisting of three consecutive Uâ¢U base pairs is located in stem-loop 1 of the 3'-UTR. We combined NMR-spectroscopy and MD-simulations to investigate its structure and dynamics. All three Uâ¢U base pairs feature two direct hydrogen bonds and are as stable as Watson-Crick AU base pairs. Plasmodium falciparum 25S rRNA contains a triple Uâ¢U mismatch motif (Pf-motif) differing from SL1-motif only with respect to the orientation of the two closing base pairs. Interestingly, while the geometry of the outer two Uâ¢U mismatches was identical in both motifs the preferred orientation of the central Uâ¢U mismatch was different. MD simulations and potassium ion titrations revealed that the potassium ion-binding mode to the major groove is connected to the different preferred geometries of the central base pair in the two motifs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA Viral
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Regiões 3' não Traduzidas
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Pareamento Incorreto de Bases
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Motivos de Nucleotídeos
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SARS-CoV-2
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article