TY - JOUR
T1 - To splice or not to splice
T2 - pseudoexons in neurological disease and opportunities for intervention
AU - Fletcher, Sue
AU - Keegan, Niall P.
AU - Mejzini, Rita
AU - Pitout, Ianthe L.
PY - 2025/6
Y1 - 2025/6
N2 - Accurate exon selection and processing of pre-messenger RNA are crucial for normal gene expression. Mutations that alter splicing disrupt pre-mRNA processing and can have diverse effects on transcript structure, making the consequences of many such mutations difficult to predict. While next-generation sequencing technologies have transformed genetic diagnosis for many patients, deep intronic variants generally evade detection and characterisation. Of all the known types of splicing mutations, the most elusive to predict are those that activate pseudoexons. Because transcripts that contain pseudoexons are otherwise generally intact, exclusion (or 'skipping') of the pseudoexon during processing of the premRNA is likely to generate a normal, functional mRNA. Characterisation of pseudoexon mutations will open opportunities for the development of antisense oligonucleotide strategies to overcome these disease-causing mutations.
AB - Accurate exon selection and processing of pre-messenger RNA are crucial for normal gene expression. Mutations that alter splicing disrupt pre-mRNA processing and can have diverse effects on transcript structure, making the consequences of many such mutations difficult to predict. While next-generation sequencing technologies have transformed genetic diagnosis for many patients, deep intronic variants generally evade detection and characterisation. Of all the known types of splicing mutations, the most elusive to predict are those that activate pseudoexons. Because transcripts that contain pseudoexons are otherwise generally intact, exclusion (or 'skipping') of the pseudoexon during processing of the premRNA is likely to generate a normal, functional mRNA. Characterisation of pseudoexon mutations will open opportunities for the development of antisense oligonucleotide strategies to overcome these disease-causing mutations.
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=uwapure5-25&SrcAuth=WosAPI&KeyUT=WOS:001459652200001&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1016/j.gde.2025.102343
DO - 10.1016/j.gde.2025.102343
M3 - Review article
C2 - 40158386
SN - 0959-437X
VL - 92
JO - Current Opinion in Genetics and Development
JF - Current Opinion in Genetics and Development
M1 - 102343
ER -