Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects

ME Rogalska, C Vivori, J Valcárcel - Nature Reviews Genetics, 2023 - nature.com
The removal of introns from mRNA precursors and its regulation by alternative splicing are
key for eukaryotic gene expression and cellular function, as evidenced by the numerous …

Scalable functional assays for the interpretation of human genetic variation

D Tabet, V Parikh, P Mali, FP Roth… - Annual Review of …, 2022 - annualreviews.org
Scalable sequence–function studies have enabled the systematic analysis and cataloging of
hundreds of thousands of coding and noncoding genetic variants in the human genome …

CRISPR/Cas9-based split homing gene drive targeting doublesex for population suppression of the global fruit pest Drosophila suzukii

AK Yadav, C Butler, A Yamamoto… - Proceedings of the …, 2023 - National Acad Sciences
Genetic-based methods offer environmentally friendly species-specific approaches for
control of insect pests. One method, CRISPR homing gene drive that target genes essential …

Splicing in the diagnosis of rare disease: advances and challenges

J Lord, D Baralle - Frontiers in genetics, 2021 - frontiersin.org
Mutations which affect splicing are significant contributors to rare disease, but are frequently
overlooked by diagnostic sequencing pipelines. Greater ascertainment of pathogenic …

[HTML][HTML] Efficient exon skip** by base-editor-mediated abrogation of exonic splicing enhancers

H Qiu, G Li, J Yuan, D Yang, Y Ma, F Wang, Y Dai… - Cell Reports, 2023 - cell.com
Duchenne muscular dystrophy (DMD) is a severe genetic disease caused by the loss of the
dystrophin protein. Exon skip** is a promising strategy to treat DMD by restoring truncated …

High-throughput mutagenesis identifies mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance

M Cortés-López, L Schulz, M Enculescu… - Nature …, 2022 - nature.com
Following CART-19 immunotherapy for B-cell acute lymphoblastic leukaemia (B-ALL), many
patients relapse due to loss of the cognate CD19 epitope. Since epitope loss can be caused …

All exons are not created equal—exon vulnerability determines the effect of exonic mutations on splicing

LL Holm, TK Doktor, KK Flugt… - Nucleic Acids …, 2024 - academic.oup.com
It is now widely accepted that aberrant splicing of constitutive exons is often caused by
mutations affecting cis-acting splicing regulatory elements (SREs), but there is a …

Benchmarking splice variant prediction algorithms using massively parallel splicing assays

C Smith, JO Kitzman - Genome Biology, 2023 - Springer
Background Variants that disrupt mRNA splicing account for a sizable fraction of the
pathogenic burden in many genetic disorders, but identifying splice-disruptive variants …

An intronic RNA element modulates Factor VIII exon-16 splicing

V Tse, G Chacaltana, M Gutierrez… - Nucleic Acids …, 2024 - academic.oup.com
Pathogenic variants in the human Factor VIII (F8) gene cause Hemophilia A (HA). Here, we
investigated the impact of 97 HA-causing single-nucleotide variants on the splicing of 11 …

Mechanism and modeling of human disease-associated near-exon intronic variants that perturb RNA splicing

HL Chiang, YT Chen, JY Su, HN Lin, CHA Yu… - Nature Structural & …, 2022 - nature.com
Abstract It is estimated that 10%–30% of disease-associated genetic variants affect splicing.
Splicing variants may generate deleteriously altered gene product and are potential …