Projects per year
Abstract
Eukaryotic genes are interrupted by introns that are removed from transcribed RNAs by splicing. Patterns of splicing complexity differ between species, but it is unclear how these differences arise. We used inter-species association mapping with Saccharomycotina species to correlate splicing signal phenotypes with the presence or absence of splicing factors. Here we show that variation in 5’ splice site sequence preferences correlate with the presence of the U6 snRNA N6-methyladenosine methyltransferase METTL16 and the splicing factor SNRNP27K. The greatest variation in 5’ splice site sequence occurred at the +4 position and involved a preference switch between adenosine and uridine. Loss of METTL16 and SNRNP27K orthologs, or a single SNRNP27K methionine residue, was associated with a preference for +4U. These findings are consistent with splicing analyses of mutants defective in either METTL16 or SNRNP27K orthologs and models derived from spliceosome structures, demonstrating that inter-species association mapping is a powerful orthogonal approach to molecular studies. We identified variation between species in the occurrence of two major classes of 5’ splice sites, defined by distinct interaction potentials with U5 and U6 snRNAs, that correlates with intron number. We conclude that variation in concerted processes of 5’ splice site selection by U6 snRNA is associated with evolutionary changes in splicing signal phenotypes.
Original language | English |
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Article number | e91997 |
Number of pages | 25 |
Journal | eLife |
Volume | 12 |
Early online date | 3 Oct 2023 |
DOIs | |
Publication status | Published - 17 Oct 2023 |
Keywords
- C. elegans
- RNA modification
- S. cerevisiae
- S. pombe
- computational biology
- evolution
- genetics
- genomics
- human
- interspecies association mapping
- m6A
- phylogenetics
- splicing
- systems biology
ASJC Scopus subject areas
- General Biochemistry,Genetics and Molecular Biology
- General Immunology and Microbiology
- General Neuroscience
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Dive into the research topics of 'Inter-species association mapping links splice site evolution to METTL16 and SNRNP27K'. Together they form a unique fingerprint.Projects
- 2 Active
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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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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