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

Quantitative profiling of pseudouridylation landscape in the human transcriptome

“…It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted October 25, 2022. ; https://doi.org/10.1101/2022.10. 25.513650 doi: bioRxiv preprint modulate alternative pre-mRNA processing 14 . Some functions of PUS are independent of their activity, for instance, pseudouridine synthase 10 (PUS10) play a role in miRNA biogenesis by promoting pri-miRNA processing, which is independent of its catalytic activity 15 .…”

“…In addition, PUS7-mediated Ψ modification inhibits codon-specific translation of tRNAs in glioblastoma and catalytic inhibition of PUS7 can reduce tumorigenesis 13 . PUS1, PUS7 and RPUSD4 have been found to modify human pre-mRNA co-transcriptionally and modulate alternative pre-mRNA processing 14 . Some functions of PUS are independent of their activity, for instance, pseudouridine synthase 10 (PUS10) play a role in miRNA biogenesis by promoting pri-miRNA processing, which is independent of its catalytic activity 15 .…”

Decoding pseudouridine: an emerging target for therapeutic development

“…There is also a significant enrichment of Ψ in RNA-binding protein (RBP) binding sites, including RBPs critical for splicing. In line with these observations, knockout of a single Ψ synthase, such as PUS1, leads to thousands of alternative splicing events, although indirect regulation may also be impacting the observed change [35].…”

“…From the perspective of a pre-mRNA molecule, Ψ may regulate splicing by influencing the local RNA structure and flexibility, thus affecting pre-mRNA interactions with the spliceosomal machinery [34]. In pre-mRNA, Ψ is installed cotranscriptionally and found in intronic elements critical for splicing, including those that directly base pair with U1 and U2 snRNAs [35]. Moreover, Ψ is enriched in elements associated with alternative splicing, such as retained introns and cassette exons.…”

Opportunities and Challenges to Profile mRNA Modifications in Escherichia coli**

“…[5,6] N 6 -methyladenosine (m 6 A) is the most abundant mRNA modification in eukaryotes and is the best studied example of how mRNA methylation regulates both mRNA stability and gene expression. [7] Pseudouridine (Ψ), one of the most abundant modifications found in all types of RNA, is also present in the coding sequence of mRNAs and has been reported to affect pre-mRNA splicing, [8] translational speed and tRNA selection by ribosomes. [9] In general, studies of the epitranscriptome utilize sophisticated sequencing approaches which allow sequence-specific localization of the RNA modification of interest.…”