Targeted pseudouridylation: An approach for suppressing nonsense mutations in disease genes

Adachi, Hironori; Pan, Yi; He, Xueyang; Chen, Jonathan L.; Klein, Bart; Platenburg, Gerard; Morais, Pedro; Boutz, Paul L.; Yu, Yi‐Tao

doi:10.1016/j.molcel.2023.01.009

Cited by 35 publications

(23 citation statements)

References 76 publications

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“…28 Additionally, instances of mRNA target pseudouridylation guided by engineered snoRNA have shed light on the potential for snoRNA-guided pseudouridylation of mRNA. 29,30 Nevertheless, further research is required to determine whether endogenous snoRNAs can guide mRNA pseudouridylation.…”

Section: Rna-guided Pseudouridylationmentioning

confidence: 99%

“…To enhance the programmable pseudouridylation efficiency, both research groups implemented novel strategies. Adachi et al 29 used an RNA polymerase II promoter-driven intronencoded construct to extend the half-life of the artificial box H/ ACA RNA, enabling sustained nonsense suppression. Song et al 30 conducted a systematic screening of hundreds of snoRNA scaffolds and modulated base-pairing length, revealing the scaffold's influence on readthrough efficiency.…”

Section: Programmable Rna Pseudouridylationmentioning

confidence: 99%

“…While H/ACA s(no)RNA-guided tRNA and mRNA pseudouridylation in eukaryotes and archaea have not been extensively studied, computational predictions and experimental evidence suggest their possible existence. − Notably, a highly parallel reporter-based approach has been employed to investigate snoRNA-guided pseudouridylation of mRNA, revealing that such modifications indeed occur . Additionally, instances of mRNA target pseudouridylation guided by engineered snoRNA have shed light on the potential for snoRNA-guided pseudouridylation of mRNA. , Nevertheless, further research is required to determine whether endogenous snoRNAs can guide mRNA pseudouridylation.…”

Section: The Biogenesis and Functions Of Rna-guided Rna Modificationsmentioning

confidence: 99%

“…While the effect of Ψ in sense codons remains controversial, it surprisingly suppresses translation termination when substituted for U in all three stop codons. Two studies , leveraged artificial box H/ACA snoRNA-guided pseudouridylation to achieve Ψ modification at premature termination codons (PTCs) in mammalian cells. They developed RESTART and targeted PTC pseudouridylation for efficient and precise pseudouridylation (Figure B).…”

Section: Applications Of Rna-guided Rna Modificationsmentioning

confidence: 99%

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RNA-Guided RNA Modifications: Biogenesis, Functions, and Applications

Li,

Qu,

Yang

2023

Acc. Chem. Res.

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Section: Rna-guided Pseudouridylationmentioning

confidence: 99%

Section: Programmable Rna Pseudouridylationmentioning

confidence: 99%

Section: The Biogenesis and Functions Of Rna-guided Rna Modificationsmentioning

confidence: 99%

Section: Applications Of Rna-guided Rna Modificationsmentioning

confidence: 99%

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RNA-Guided RNA Modifications: Biogenesis, Functions, and Applications

Li,

Qu,

Yang

2023

Acc. Chem. Res.

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“…The most well-established function of mRNA pseudouridylation is to promote translational readthrough of Ψ-modified stop codons (ΨAA, ΨAG, and ΨGA) . Taking advantage of targeted pseudouridylation by the RNA-guided DKC1 modification machinery, we and others have installed site-specific Ψs in the premature termination codons of mRNA, which are transcribed from genes with disease-causing nonsense mutations. , Hence, novel programmable RNA base editors have been developed thanks to our improved understanding of Ψ writer proteins.…”

Section: Pseudouridine: the Most Abundant Rna Modificationmentioning

confidence: 99%

Quantifying m⁶A and Ψ Modifications in the Transcriptome via Chemical-Assisted Approaches

Zhang,

Xiao,

Jiang

et al. 2023

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: Since the discovery of the first chemically modified RNA nucleotide in 1951, more than 170 types of chemical modifications have been characterized in RNA so far.Since the discovery of the reversible and dynamic nature of N 6methyladenosine (m 6 A) in mRNA modification, researchers have identified about ten modifications in eukaryotic mRNA; together with modifications on the noncoding RNAs, the term "epitranscriptome" has been coined to describe the ensemble of various chemical RNA modifications. The past decade has witnessed the discovery of many novel molecular functions of mRNA modifications, demonstrating their crucial roles in gene expression regulation. As the most abundant modifications in mRNA, the study of m 6 A and Ψ has been facilitated by innovative highthroughput sequencing technologies, which can be based on antibodies, enzymes, or novel chemistry. Among them, chemicalassisted methods utilize selective chemistry that can discriminate modified versus unmodified nucleotides, enabling the transcriptome-wide mapping of m 6 A and Ψ modifications and functional studies.Our group has developed several sequencing technologies to investigate these epitranscriptomic marks including m 6 A, Ψ, m 1 A, and m 6 Am. Among them, we have recently developed two methods for absolute quantification of m 6 A and Ψ in the transcriptome based on chemical reactivity to distinguish and measure the two modifications. In GLORI, we used glyoxal and nitrite to mediate efficient deamination of regular adenosine, while m 6 A remained unaffected, thereby enabling efficient and unbiased detection of single-base resolution and absolute quantification of m 6 A modification. In CeU-seq and PRAISE, we used different chemistry to achieve selective labeling and detection of transcriptome-wide Ψ. CeU-seq is based on an azido-derivatized carbodiimide compound, while PRAISE utilizes the unique activity of bisulfite to Ψ. PRAISE results in the formation of ring-opening Ψ-bisulfite adduct and quantitatively detects Ψ as 1−2 nt deletion signatures during sequencing. The resulting base-resolution and stoichiometric information expanded our understanding to the profiles of RNA modifications in the transcriptome. In particular, the quantitative information on RNA methylome is critical for characterizing the dynamic and reversible nature of RNA modifications, for instance, under environmental stress or during development. Additionally, base-resolution and stoichiometric information can greatly facilitate the analysis and characterization of functional modification sites that are important for gene expression regulation, especially when one modification type may have multiple or even opposing functions within a specific transcript. Together, the quantitative profiling methods provide the modification stoichiometry information, which is critical to study the regulatory roles of RNA modifications.In this Account, we will focus on the quantitative sequencing technologies of m 6 A and Ψ developed in our g...

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Engineered RNA‐Binding Proteins: Studying and Controlling RNA Regulation

Sinnott,

Cao,

Dickinson

2024

Israel Journal of Chemistry

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The complexity of eukaryotic organisms is intricately tied to transcriptome‐level processes, notably alternative splicing and the precise modulation of gene expression through a sophisticated interplay involving RNA‐binding protein (RBP) networks and their RNA targets. Recent advances in our understanding of the molecular pathways responsible for this control have paved the way for the development of tools capable of steering and managing RNA regulation and gene expression. The fusion between a rapidly developing understanding of endogenous RNA regulation and the burgeoning capabilities of CRISPR‐Cas and other programmable RBP platforms has given rise to an exciting frontier in engineered RNA regulators. This review offers an overview of the existing toolkit for constructing synthetic RNA regulators using programmable RBPs and effector domains, capable of altering RNA sequence composition or fate, and explores their diverse applications in both basic research and therapeutic contexts.

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Targeted pseudouridylation: An approach for suppressing nonsense mutations in disease genes

Cited by 35 publications

References 76 publications

RNA-Guided RNA Modifications: Biogenesis, Functions, and Applications

RNA-Guided RNA Modifications: Biogenesis, Functions, and Applications

Quantifying m⁶A and Ψ Modifications in the Transcriptome via Chemical-Assisted Approaches

Engineered RNA‐Binding Proteins: Studying and Controlling RNA Regulation

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Targeted pseudouridylation: An approach for suppressing nonsense mutations in disease genes

Cited by 35 publications

References 76 publications

RNA-Guided RNA Modifications: Biogenesis, Functions, and Applications

RNA-Guided RNA Modifications: Biogenesis, Functions, and Applications

Quantifying m6A and Ψ Modifications in the Transcriptome via Chemical-Assisted Approaches

Engineered RNA‐Binding Proteins: Studying and Controlling RNA Regulation

Contact Info

Product

Resources

About

Quantifying m⁶A and Ψ Modifications in the Transcriptome via Chemical-Assisted Approaches