m6A modification of U6 snRNA modulates usage of two major classes of pre-mRNA 5' splice site
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
m6A modification of U6 snRNA modulates usage of two major classes of pre-mRNA 5' splice site. / Parker, Matthew T.; Soanes, Beth K.; Kusakina, Jelena; Larrieu, Antoine; Knop, Katarzyna; Joy, Nisha; Breidenbach, Friedrich; Sherwood, Anna; Barton, Geoffrey J.; Fica, Sebastian M.; Davies, Brendan H.; Simpson, Gordon G.
I: eLife, Bind 11, 78808, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - m6A modification of U6 snRNA modulates usage of two major classes of pre-mRNA 5' splice site
AU - Parker, Matthew T.
AU - Soanes, Beth K.
AU - Kusakina, Jelena
AU - Larrieu, Antoine
AU - Knop, Katarzyna
AU - Joy, Nisha
AU - Breidenbach, Friedrich
AU - Sherwood, Anna
AU - Barton, Geoffrey J.
AU - Fica, Sebastian M.
AU - Davies, Brendan H.
AU - Simpson, Gordon G.
PY - 2022
Y1 - 2022
N2 - 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 N-6 methylation, but the role of this m(6)A modification is poorly understood. Here, we show that m(6)A modified U6 snRNA determines the accuracy and efficiency of splicing. We reveal that the conserved methyltransferase, FIONA1, is required for Arabidopsis U6 snRNA m(6)A 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 m(6)A 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 m(6)A modification contributes to the selection of degenerate 5' splice sites crucial to alternative splicing.
AB - 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 N-6 methylation, but the role of this m(6)A modification is poorly understood. Here, we show that m(6)A modified U6 snRNA determines the accuracy and efficiency of splicing. We reveal that the conserved methyltransferase, FIONA1, is required for Arabidopsis U6 snRNA m(6)A 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 m(6)A 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 m(6)A modification contributes to the selection of degenerate 5' splice sites crucial to alternative splicing.
KW - splicing
KW - epitranscriptome
KW - m6A
KW - flowering time
KW - ambient temperature
KW - A
KW - thaliana
KW - C
KW - elegans
KW - D
KW - melanogaster
KW - Human
KW - Zebrafish
KW - SMALL NUCLEAR RNAS
KW - CRYO-EM STRUCTURE
KW - N-6-ADENOSINE METHYLATION
KW - REFERENCE GENOME
KW - ARABIDOPSIS
KW - N-6-METHYLADENOSINE
KW - SEQUENCE
KW - METTL16
KW - METHYLTRANSFERASE
KW - TRANSCRIPTION
U2 - 10.7554/eLife.78808
DO - 10.7554/eLife.78808
M3 - Journal article
C2 - 36409063
VL - 11
JO - eLife
JF - eLife
SN - 2050-084X
M1 - 78808
ER -
ID: 338533197