RNA Splicing: A split consensus reveals two major 5’ splice site classes

Matthew T. Parker; Sebastian M Fica; Gordon Simpson

doi:10.1098/rsob.240293

RNA Splicing: A split consensus reveals two major 5’ splice site classes

Matthew T. Parker, Sebastian M Fica, Gordon Simpson (Lead / Corresponding author)

Plant Sciences

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Abstract

The established consensus sequence for human 5’ splice sites masks the presence of two major splice site classes defined by preferential base-pairing potentials with either U5 snRNA loop 1 or the U6 snRNA ACAGA box. The two 5’ splice site classes are separable in genome sequences, sensitised by specific genotypes, and associated with splicing complexity. The two classes reflect the commitment to 5’ splice site usage occurring primarily during 5’ splice site transfer to U6 snRNA. Separating the human 5’ splice site consensus into its two major constituents can help us understand fundamental features of eukaryote genome architecture and splicing mechanisms and inform treatment design for diseases caused by genetic variation affecting splicing.

Original language	English
Number of pages	12
Journal	Open Biology
Volume	15
Issue number	1
DOIs	https://doi.org/10.1098/rsob.240293
Publication status	Published - 15 Jan 2025

Keywords

Splicing
METTL16
SNRNP27K
m6A
T-loop
Spliceosome
mRNA
Evolution
Eukaryote
ReNu syndrome

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1098/rsob.240293Licence: CC BY

Final Published VersionFinal published version, 1.87 MBLicence: CC BY

1 Finished
1 Active

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
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

Cite this

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title = "RNA Splicing: A split consensus reveals two major 5{\textquoteright} splice site classes",

abstract = "The established consensus sequence for human 5{\textquoteright} splice sites masks the presence of two major splice site classes defined by preferential base-pairing potentials with either U5 snRNA loop 1 or the U6 snRNA ACAGA box. The two 5{\textquoteright} splice site classes are separable in genome sequences, sensitised by specific genotypes, and associated with splicing complexity. The two classes reflect the commitment to 5{\textquoteright} splice site usage occurring primarily during 5{\textquoteright} splice site transfer to U6 snRNA. Separating the human 5{\textquoteright} splice site consensus into its two major constituents can help us understand fundamental features of eukaryote genome architecture and splicing mechanisms and inform treatment design for diseases caused by genetic variation affecting splicing.",

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AU - Fica, Sebastian M

AU - Simpson, Gordon

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N2 - The established consensus sequence for human 5’ splice sites masks the presence of two major splice site classes defined by preferential base-pairing potentials with either U5 snRNA loop 1 or the U6 snRNA ACAGA box. The two 5’ splice site classes are separable in genome sequences, sensitised by specific genotypes, and associated with splicing complexity. The two classes reflect the commitment to 5’ splice site usage occurring primarily during 5’ splice site transfer to U6 snRNA. Separating the human 5’ splice site consensus into its two major constituents can help us understand fundamental features of eukaryote genome architecture and splicing mechanisms and inform treatment design for diseases caused by genetic variation affecting splicing.

AB - The established consensus sequence for human 5’ splice sites masks the presence of two major splice site classes defined by preferential base-pairing potentials with either U5 snRNA loop 1 or the U6 snRNA ACAGA box. The two 5’ splice site classes are separable in genome sequences, sensitised by specific genotypes, and associated with splicing complexity. The two classes reflect the commitment to 5’ splice site usage occurring primarily during 5’ splice site transfer to U6 snRNA. Separating the human 5’ splice site consensus into its two major constituents can help us understand fundamental features of eukaryote genome architecture and splicing mechanisms and inform treatment design for diseases caused by genetic variation affecting splicing.

KW - Splicing

KW - METTL16

KW - SNRNP27K

KW - m6A

KW - T-loop

KW - Spliceosome

KW - mRNA

KW - Evolution

KW - Eukaryote

KW - ReNu syndrome

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DO - 10.1098/rsob.240293

M3 - Article

C2 - 39809319

SN - 2046-2441

VL - 15

JO - Open Biology

JF - Open Biology

IS - 1

ER -

RNA Splicing: A split consensus reveals two major 5’ splice site classes

Abstract

Keywords

UN SDGs

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Projects

Temperature Responsive Control of Splicing by RNA Methylation (Joint with University of Leeds)

Control of PolyA Site Choice by m6A RNA Modification

Cite this