RNA splicing articles from across Nature Portfolio

Here, the authors describe a noncoding genetic variant in GBA1 specific to people of African ancestry that increases the risk of neurodegenerative diseases by interfering with the splicing of mRNA, resulting in lowered protein levels and activity.

A transformer-based method efficiently detects RNA splicing from 45,000-nucleotide sequences by applying hard attention to select splice site candidates, outperforming SpliceAI in identifying splice sites and disease-related variants.

Exon skipping technologies remain hindered by aberrant splicing and low efficacy. Here, Miskalis et.al. developed SPLICER, a Cas9 base editor toolbox which enhances overall exon skipping efficiency and lowers cryptic splicing, demonstrating the use of SPLICER for skipping APP exon 17 in a mouse model of Alzheimer’s disease.

Here the authors identify GPATCH11 variants responsible for retinal dystrophy with neurological impairment and facial dysmorphy. They explore its function using a mouse model and demonstrate GPATCH11’s involvement in RNA regulation and splicing.

RNA splicing is crucial for gene expression diversity and can be altered by mutations. Here, the authors present SpTransformer, a deep learning tool that predicts tissue-specific RNA splicing with high accuracy, revealing splicing’s role in pathogenic mutations and aiding clinical interpretations.

A new study combines massively parallel assays, transcriptomics and biophysical modeling to provide a framework for analyzing the effects of compounds that modulate pre-mRNA splicing. The results lend important insights into the mechanisms of drug action and facilitate the design of splicing therapies.

Spliceosome biogenesis and recycling remains a largely unexplored area. Two papers now reveal how protein chaperones remodel the 20S U5 snRNP, leading to formation of the U4/U6.U5 tri-snRNP.

In the first comprehensive mRNA isoform atlas of the developing and adult mouse brain, we discover that region and age influence the isoform repertoire of cell subtypes. We link peak cell type regulation to the critical development period and report attenuated levels in adulthood.

The requirement for a protospacer adjacent motif (PAM) is a well-known limitation of the CRISPR–Cas9 system, as it restricts the range of sequences that can be targeted. To address this limitation, we demonstrate a phage-assisted evolution approach for engineering a compact SlugCas9, simplifying its PAM requirement and broadening its DNA targeting scope.