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Inter-species association mapping links splice site evolution to METTL16 and SNRNP27K

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...

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Autores principales: Parker, Matthew T, Fica, Sebastian M, Barton, Geoffrey J, Simpson, Gordon G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581693/
https://www.ncbi.nlm.nih.gov/pubmed/37787376
http://dx.doi.org/10.7554/eLife.91997
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author Parker, Matthew T
Fica, Sebastian M
Barton, Geoffrey J
Simpson, Gordon G
author_facet Parker, Matthew T
Fica, Sebastian M
Barton, Geoffrey J
Simpson, Gordon G
author_sort Parker, Matthew T
collection PubMed
description 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 +4 U. 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.
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spelling pubmed-105816932023-10-18 Inter-species association mapping links splice site evolution to METTL16 and SNRNP27K Parker, Matthew T Fica, Sebastian M Barton, Geoffrey J Simpson, Gordon G eLife Computational and Systems Biology 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 +4 U. 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. eLife Sciences Publications, Ltd 2023-10-03 /pmc/articles/PMC10581693/ /pubmed/37787376 http://dx.doi.org/10.7554/eLife.91997 Text en © 2023, Parker et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Computational and Systems Biology
Parker, Matthew T
Fica, Sebastian M
Barton, Geoffrey J
Simpson, Gordon G
Inter-species association mapping links splice site evolution to METTL16 and SNRNP27K
title Inter-species association mapping links splice site evolution to METTL16 and SNRNP27K
title_full Inter-species association mapping links splice site evolution to METTL16 and SNRNP27K
title_fullStr Inter-species association mapping links splice site evolution to METTL16 and SNRNP27K
title_full_unstemmed Inter-species association mapping links splice site evolution to METTL16 and SNRNP27K
title_short Inter-species association mapping links splice site evolution to METTL16 and SNRNP27K
title_sort inter-species association mapping links splice site evolution to mettl16 and snrnp27k
topic Computational and Systems Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581693/
https://www.ncbi.nlm.nih.gov/pubmed/37787376
http://dx.doi.org/10.7554/eLife.91997
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