Topic
Pseudouridine
About: Pseudouridine is a research topic. Over the lifetime, 891 publications have been published within this topic receiving 35628 citations. The topic is also known as: Psi-uridine & (1S)-1,4-anhydro-1-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-D-ribitol.
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TL;DR: It is concluded that nucleoside modifications suppress the potential of RNA to activate DCs, and the innate immune system may detect RNA lacking nucleosides modification as a means of selectively responding to bacteria or necrotic tissue.
1,582 citations
TL;DR: It is found that mRNAs containing pseudouridines have a higher translational capacity than unmodified m RNAs when tested in mammalian cells and lysates or administered intravenously into mice at 0.015-0.15 mg/kg doses.
1,101 citations
TL;DR: Gilbert et al. as discussed by the authors used pseudouridylation detection on a genome-wide scale, leading to the identification of pseudouridine in messenger RNAs as well as almost 100 new sites in non-coding RNAs.
Abstract: The modification of uridine to pseudouridine is widespread in transfer and ribosomal RNAs but not observed so far in a coding RNA; here a new technique is used to detect this modification on a genome-wide scale, leading to the identification of pseudouridylation in messenger RNAs as well as almost 100 new sites in non-coding RNAs. The modification of uridine to pseudouridine is widespread in transfer and ribosomal RNAs. Until now it had not been identified in a coding RNA. Wendy Gilbert and colleagues have employed a next-generation sequencing technique called Pseudo-seq to measure the uridine-to-pseudouridine modification on a genome-wide scale. They not only identify almost 100 new sites in non-coding RNAs, but also discover pseudouridylation in mRNAs. These modifications are mostly due to the activity of the Pus pseudouridine synthase family members, and they can be responsive to environmental conditions, suggesting that inducible modification of RNA might be another way to regulate transcription. Post-transcriptional modification of RNA nucleosides occurs in all living organisms. Pseudouridine, the most abundant modified nucleoside in non-coding RNAs1, enhances the function of transfer RNA and ribosomal RNA by stabilizing the RNA structure2,3,4,5,6,7,8. Messenger RNAs were not known to contain pseudouridine, but artificial pseudouridylation dramatically affects mRNA function—it changes the genetic code by facilitating non-canonical base pairing in the ribosome decoding centre9,10. However, without evidence of naturally occurring mRNA pseudouridylation, its physiological relevance was unclear. Here we present a comprehensive analysis of pseudouridylation in Saccharomyces cerevisiae and human RNAs using Pseudo-seq, a genome-wide, single-nucleotide-resolution method for pseudouridine identification. Pseudo-seq accurately identifies known modification sites as well as many novel sites in non-coding RNAs, and reveals hundreds of pseudouridylated sites in mRNAs. Genetic analysis allowed us to assign most of the new modification sites to one of seven conserved pseudouridine synthases, Pus1–4, 6, 7 and 9. Notably, the majority of pseudouridines in mRNA are regulated in response to environmental signals, such as nutrient deprivation in yeast and serum starvation in human cells. These results suggest a mechanism for the rapid and regulated rewiring of the genetic code through inducible mRNA modifications. Our findings reveal unanticipated roles for pseudouridylation and provide a resource for identifying the targets of pseudouridine synthases implicated in human disease11,12,13.
733 citations
TL;DR: In this paper, the authors develop Ψ-seq for transcriptome-wide quantitative mapping of pseudouridine and identify hundreds of unique sites in human and yeast mRNAs and snoRNAs.
697 citations
TL;DR: It is demonstrated that site-specific pseudouridylation of rRNAs relies on short ribosomal signal sequences that are complementary to sequences in box H/ACA snoRNAs.
636 citations