Pseudouridines in RNAs: switching atoms means shifting paradigms

Lin, Ting‐Yu; Mehta, Rahul; Glatt, Sebastian

doi:10.1002/1873-3468.14188

Cited by 24 publications

(19 citation statements)

References 100 publications

(153 reference statements)

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“…Better thermal stability. Ψ-A, Ψ-G, Ψ-U, and Ψ-C pairs are formed at several sites in structured RNAs that are conserved across species to stabilize important RNA duplexes and improve RNA-protein interactions (Lin et al, 2021).…”

Section: Pseudouridylationmentioning

confidence: 99%

The essential roles of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis

Cai

Wang

Han

et al. 2023

Front. Mol. Biosci.

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Hematopoietic stem cells (HSCs) developing from mesoderm during embryogenesis are important for the blood circulatory system and immune system. Many factors such as genetic factors, chemical exposure, physical radiation, and viral infection, can lead to the dysfunction of HSCs. Hematological malignancies (involving leukemia, lymphoma, and myeloma) were diagnosed in more than 1.3 million people globally in 2021, taking up 7% of total newly-diagnosed cancer patients. Although many treatments like chemotherapy, bone marrow transplantation, and stem cell transplantation have been applied in clinical therapeutics, the average 5-year survival rate for leukemia, lymphoma, and myeloma is about 65%, 72%, and 54% respectively. Small non-coding RNAs play key roles in a variety of biological processes, including cell division and proliferation, immunological response and cell death. With the development of technologies in high-throughput sequencing and bioinformatic analysis, there is emerging research about modifications on small non-coding RNAs, as well as their functions in hematopoiesis and related diseases. In this study, we summarize the updated information of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis, which sheds lights into the future application of HSCs into the treatment of blood diseases.

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Section: Pseudouridylationmentioning

confidence: 99%

The essential roles of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis

Cai

Wang

Han

et al. 2023

Front. Mol. Biosci.

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“…The key modification turned out to be the replacement of uridine residues with pseudouridine (Psi), the most common RNA modification, for example occurring in nonimmunogenic RNAs, such as transfer RNAs or ribosomal RNAs [56]. At the molecular level, Lin and colleagues showed that Psi residues establish additional bonds with neighbouring atoms and thereby strengthen RNA–RNA and RNA–protein interactions [57]. In case of messenger RNA, the presence of Psi sites enhances the lifetime and the translation efficiency of the mRNA and reduces unwanted innate immune reactions, such as inflammation.…”

Section: Covid Vaccines and Mrnamentioning

confidence: 99%

Two years into COVID‐19 – Lessons in SARS‐CoV‐2 and a perspective from papers in FEBS Letters

Greber

2021

FEBS Letters

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The 2019 outbreak of coronavirus disease in Wuhan (Hubei province of China) has given rise to a pandemic spread of virus, more than 240 million incidences and a death toll larger than 5 million people. COVID-19 has set off large efforts in research, therapy and patient care, as well as public and private debates in every imaginable form. A number of scientists used the publication platforms provided by the Federation of the European Biochemical Societies (FEBS) to present their research data, reviews, opinions and other contributions relating to COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, I highlight the recent COVID-19 papers which have been published and collected in a Virtual Issue in FEBS Letters, and discuss their implications towards understanding the molecular, biochemical and cellular mechanisms of SARS-CoV-2 infections, vaccine development and antiviral discovery strategies.

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“…The detection of Ψ is based on the selective labeling by N3‐[ N ‐cyclohexyl‐ N ′‐β‐(4‐methylmorpholinium)ethylcarbodiimide (CMC), which can be identified by reverse transcription or next‐generation sequencing (NGS) techniques (T. Y. Lin et al, 2021 ). Recently it was shown, that nanopore sequencing might offer the possibility of a label‐free method to detect and quantify the incorporation of Ψ in different types of RNAs (Begik et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Destabilization of mutated human PUS3 protein causes intellectual disability

et al. 2022

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Pseudouridine (Ψ) is an RNA base modification ubiquitously found in many types of RNAs. In humans, the isomerization of uridine is catalyzed by different stand-alone pseudouridine synthases (PUS). Genomic mutations in the human pseudouridine synthase 3 gene (PUS3) have been identified in patients with neurodevelopmental disorders. However, the underlying molecular mechanisms that cause the disease phenotypes remain elusive. Here, we utilize exome sequencing to identify genomic variants that lead to a homozygous amino acid substitution (p.[(Tyr71Cys)];[(-Tyr71Cys)]) in human PUS3 of two affected individuals and a compound heterozygous substitution (p.[(Tyr71Cys)];[(Ile299Thr)]) in a third patient. We obtain wild-type and mutated full-length human recombinant PUS3 proteins and characterize the enzymatic activity in vitro. Unexpectedly, we find that the p.Tyr71Cys substitution neither affect tRNA binding nor pseudouridylation activity in vitro, but strongly impair the thermostability profile of PUS3, while the p.Ile299Thr mutation causes protein aggregation. Concomitantly, we observe that the PUS3 protein levels as well as the level of PUS3-dependent Ψ levels are strongly reduced in fibroblasts derived from all three patients. In summary, our results directly

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Pseudouridines in RNAs: switching atoms means shifting paradigms

Abstract: Ting-Yu Lin and Rahul Mehta contributed equally to this article.

Cited by 24 publications

References 100 publications

The essential roles of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis

The essential roles of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis

Two years into COVID‐19 – Lessons in SARS‐CoV‐2 and a perspective from papers in FEBS Letters

Destabilization of mutated human PUS3 protein causes intellectual disability

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