Pseudouridine-mediated stop codon readthrough in
PTC
nonsense suppression
pseudouridylation
sequence context
stop codon
Journal
RNA (New York, N.Y.)
ISSN: 1469-9001
Titre abrégé: RNA
Pays: United States
ID NLM: 9509184
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
23
04
2020
accepted:
19
05
2020
pubmed:
22
5
2020
medline:
6
10
2020
entrez:
22
5
2020
Statut:
ppublish
Résumé
We have previously shown that when the uridine of a stop codon (UAA, UAG, or UGA) is pseudouridylated, the ribosome reads through the modified stop codon. However, it is not clear as to whether or not the pseudouridine (Ψ)-mediated readthrough is dependent on the sequence context of mRNA. Here, we use several different approaches and the yeast system to address this question. We show that when a stop codon (premature termination codon, PTC) is introduced into the coding region of a reporter mRNA at several different positions (with different sequence contexts) and pseudouridylated, we detect similar levels of readthrough. Using mutational and selection/screen analyses, we also show that the upstream sequence (relative to PTC) as well as the nucleotides surrounding the PTC (upstream and downstream) play a minimal role (if at all) in Ψ-mediated ribosome readthrough. Interestingly, we detect no suppression of NMD (nonsense-mediated mRNA decay) by targeted PTC pseudouridylation in the yeast system. Our results indicate that Ψ-mediated nonsense suppression occurs at the translational level, and that the suppression is sequence context-independent, unlike some previously characterized rare stop codon readthrough events.
Identifiants
pubmed: 32434780
pii: rna.076042.120
doi: 10.1261/rna.076042.120
pmc: PMC7430670
doi:
Substances chimiques
Codon, Nonsense
0
Codon, Terminator
0
Nucleotides
0
RNA, Messenger
0
Pseudouridine
1445-07-4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1247-1256Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM062937
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM138387
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA241111
Pays : United States
Organisme : NIH HHS
ID : S10 OD021489
Pays : United States
Informations de copyright
© 2020 Adachi and Yu; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
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