Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect splicing

2020 ◽  
Author(s):  
Nidhi Kanwal
Keyword(s):  
Pseudouridine Synthases

Pseudouridines and Pseudouridine Synthases of the Ribosome

2001 ◽  
Vol 66 (0) ◽  
pp. 147-160 ◽  
Author(s):  
J. OFENGAND ◽  
A. MALHOTRA ◽  
J. REMME ◽  
N.S. GUTGSELL ◽  
M. DEL CAMPO ◽  
...  
Keyword(s):  
Pseudouridine Synthases

scholarly journals Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect splicing

2020 ◽  
Author(s):  
Nicole M. Martinez ◽  
Amanda Su ◽  
Julia K. Nussbacher ◽  
Margaret C. Burns ◽  
Cassandra Schaening ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Genetic Manipulation ◽  
Rna Modification ◽  
Messenger Rnas ◽  
Specific Expression ◽  
Pseudouridine Synthases ◽  
In Cells

AbstractEukaryotic messenger RNAs are extensively decorated with modified nucleotides and the resulting epitranscriptome plays important regulatory roles in cells 1. Pseudouridine (Ψ) is a modified nucleotide that is prevalent in human mRNAs and can be dynamically regulated 2–5. However, it is unclear when in their life cycle RNAs become pseudouridylated and what the endogenous functions of mRNA pseudouridylation are. To determine if pseudouridine is added co-transcriptionally, we conducted pseudouridine profiling 2 on chromatin-associated RNA to reveal thousands of intronic pseudouridines in nascent pre-mRNA at locations that are significantly associated with alternatively spliced exons, enriched near splice sites, and overlap hundreds of binding sites for regulatory RNA binding proteins. Multiple distinct pseudouridine synthases with tissue-specific expression pseudouridylate pre-mRNA sites, and genetic manipulation of the predominant pre-mRNA modifying pseudouridine synthases PUS1, PUS7 and RPUSD4 induced widespread changes in alternative splicing in cells, supporting a role for pre-mRNA pseudouridylation in alternative splicing regulation. Consistently, we find that individual pseudouridines identified in cells are sufficient to directly affect splicing in vitro. Together with previously observed effects of artificial pseudouridylation on RNA-RNA6–8 and RNA-protein 9–11 interactions that are relevant for splicing, our results demonstrate widespread co-transcriptional pre-mRNA pseudouridylation and establish the enormous potential for this RNA modification to control human gene expression.

scholarly journals Loss of Pseudouridine Synthases in the RluA Family Causes Hypersensitive Nociception in Drosophila

2020 ◽  
Vol 10 (12) ◽  
pp. 4425-4438
Author(s):  
Wan Song ◽  
Susanne Ressl ◽  
W. Daniel Tracey
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Null Alleles ◽  
Rna Modification ◽  
Loss Of Function ◽  
Specific Expression ◽  
Nociceptive Neurons ◽  
Link Type ◽  
Pseudouridine Synthases ◽  
Link Loss

Nociceptive neurons of Drosophila melanogaster larvae are characterized by highly branched dendritic processes whose proper morphogenesis relies on a large number of RNA-binding proteins. Post-transcriptional regulation of RNA in these dendrites has been found to play an important role in their function. Here, we investigate the neuronal functions of two putative RNA modification genes, RluA-1 and RluA-2, which are predicted to encode pseudouridine synthases. RluA-1 is specifically expressed in larval sensory neurons while RluA-2 expression is ubiquitous. Nociceptor-specific RNAi knockdown of RluA-1 caused hypersensitive nociception phenotypes, which were recapitulated with genetic null alleles. These were rescued with genomic duplication and nociceptor-specific expression of UAS-RluA-1-cDNA. As with RluA-1, RluA-2 loss of function mutants also displayed hyperalgesia. Interestingly, nociceptor neuron dendrites showed a hyperbranched morphology in the RluA-1 mutants. The latter may be a cause or a consequence of heightened sensitivity in mutant nociception behaviors.

scholarly journals A cell-free yellow lupin extract containing activities of pseudouridine 35 and 55 synthases.

1998 ◽  
Vol 45 (3) ◽  
pp. 745-754 ◽  
Author(s):  
J Pieńkowska ◽  
J Wrzesiński ◽  
Z Szweykowska-Kulińska
Keyword(s):  
Arabidopsis Thaliana ◽  
Rna Polymerase ◽  
Seed Extract ◽  
T7 Rna Polymerase ◽  
Lupinus Luteus ◽  
Dependent Manner ◽  
Yellow Lupin ◽  
First Report ◽  
Pseudouridine Synthases ◽  
A Cell

Plant cytoplasmic tyrosine tRNA was pseudouridylated at three different positions: 35, 39 and 55. These pseudouridines were introduced by three different enzymes--pseudouridine synthases. Variants of the Arabidopsis thaliana pre-tRNA(Tyr) were constructed that allow to monitor specifically pseudouridylation at different nucleotide positions. Using such RNAs to assay pseudouridine synthesis we have prepared an extract from Lupinus luteus cv. Ventus seeds containing activities of at least psi35 and psi55 synthases. This is the first report describing the preparation of the lupin seed extract that specifically modifies plant pre-tRNA(Tyr) transcribed by T7 RNA polymerase. U35 is converted to psi35 only in an intron-dependent manner, while pseudouridylation of U55 is insensitive to the presence or absence of an intron.

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