Projects per year
Abstract
Alternative splicing of messenger RNAs is associated with the evolution of developmentally complex eukaryotes. Splicing is mediated by the spliceosome, and docking of the pre-mRNA 5' splice site into the spliceosome active site depends upon pairing with the conserved ACAGA sequence of U6 snRNA. In some species, including humans, the central adenosine of the ACAGA box is modified by N6 methylation, but the role of this m6A modification is poorly understood. Here, we show that m6A modified U6 snRNA determines the accuracy and efficiency of splicing. We reveal that the conserved methyltransferase, FIONA1, is required for Arabidopsis U6 snRNA m6A modification. Arabidopsis fio1 mutants show disrupted patterns of splicing that can be explained by the sequence composition of 5' splice sites and cooperative roles for U5 and U6 snRNA in splice site selection. U6 snRNA m6A influences 3' splice site usage. We generalise these findings to reveal two major classes of 5' splice site in diverse eukaryotes, which display anti-correlated interaction potential with U5 snRNA loop 1 and the U6 snRNA ACAGA box. We conclude that U6 snRNA m6A modification contributes to the selection of degenerate 5' splice sites crucial to alternative splicing.
Original language | English |
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Article number | e78808 |
Number of pages | 34 |
Journal | eLife |
Volume | 11 |
Early online date | 21 Nov 2022 |
DOIs | |
Publication status | Published - 30 Dec 2022 |
Keywords
- A. thaliana
- C. elegans
- D. melanogaster
- ambient temperature
- chromosomes
- epitranscriptome
- flowering time
- gene expression
- genetics
- genomics
- human
- m6A
- splicing
- zebrafish
ASJC Scopus subject areas
- General Neuroscience
- General Biochemistry,Genetics and Molecular Biology
- General Immunology and Microbiology
Fingerprint
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Temperature Responsive Control of Splicing by RNA Methylation (Joint with University of Leeds)
Simpson, G. (Investigator)
Biotechnology and Biological Sciences Research Council
19/09/22 → 18/09/25
Project: Research
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Depicting the richest source of pathogen linked miscellaneous gene expression in orphan crops by Nanopore (OCNANO)
Simpson, G. (Investigator)
COMMISSION OF THE EUROPEAN COMMUNITIES
1/09/21 → 31/08/23
Project: Research
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Control of PolyA Site Choice by m6A RNA Modification
Barton, G. (Investigator) & Simpson, G. (Investigator)
Biotechnology and Biological Sciences Research Council
1/07/21 → 13/02/25
Project: Research
Datasets
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Mutant screen of early flowering Arabidopsis EMS mutants with increased MAF2 intron retention
Parker, M. (Creator), Soanes, B. K. (Creator), Kusakina, J. (Creator), Larrieu, A. (Creator), Knop, K. (Creator), Joy, N. (Creator), Breidenbach, F. (Creator), Sherwood, A. (Creator), Barton, G. (Creator), Fica, S. M. (Creator), Davies, B. H. (Creator) & Simpson, G. (Creator), European Nucleotide Archive, 5 Apr 2022
https://www.ebi.ac.uk/ena/browser/view/PRJEB51468
Dataset
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Nanopore direct RNA sequencing of Col-0 and fio1-3 mutant Arabidopsis
Parker, M. (Creator), Soanes, B. K. (Creator), Kusakina, J. (Creator), Larrieu, A. (Creator), Knop, K. (Creator), Joy, N. (Creator), Breidenbach, F. (Creator), Sherwood, A. (Creator), Barton, G. (Creator), Fica, S. M. (Creator), Davies, B. H. (Creator) & Simpson, G. (Creator), European Nucleotide Archive, 5 Apr 2022
https://www.ebi.ac.uk/ena/browser/view/PRJEB51364
Dataset
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Illumina RNA sequencing of Col-0 and fio1-3 mutant Arabidopsis
Parker, M. (Creator), Soanes, B. K. (Creator), Kusakina, J. (Creator), Larrieu, A. (Creator), Knop, K. (Creator), Joy, N. (Creator), Breidenbach, F. (Creator), Sherwood, A. (Creator), Barton, G. (Creator), Fica, S. M. (Creator), Davies, B. H. (Creator) & Simpson, G. (Creator), European Nucleotide Archive, 5 Apr 2022
https://www.ebi.ac.uk/ena/browser/view/PRJEB51363
Dataset
Equipment
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Fingerprints Proteomics Facility
Centre for Advanced Scientific TechnologiesFacility/equipment: Facility