RNA splicing articles from across Nature Portfolio

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.

Somatic expansion of a CAG repeat in HTT drives onset of Huntington’s disease. Using a human cell line model and splice modulators, here the authors show that PMS1 is an enhancer of CAG repeat expansion, making it a target for therapeutic intervention.

RNA alternative splicing is involved in determining cell identity, but a comprehensive molecular map is missing. Here, the authors provide a human and mouse brain atlas of transcript isoforms linking them to cellular identity, brain regions and development stages.

Methodological advances have enabled discoveries of RNA polymerase interactions with RNA processing machineries, such as the splicing and 3′-end cleavage machineries. This Review discusses the roles of these interactions in gene regulation and eukaryotic cellular stress responses, and highlights parallels between co-transcriptional RNA processing in eukaryotes and prokaryotes.

The biogenesis and recycling of the ‘heart’ of the human spliceosome, the U5 small nuclear ribonucleoprotein (snRNP), requires CD2BP2 and TSSC4. Here the authors present cryo-electron microscopy structures that reveal how these protein chaperones orchestrate the ATP-independent (re)generation of the U5 snRNP.

Here the authors report the structure of the human 20S U5 snRNP, providing new insights into the assembly of the spliceosome building blocks.

RNA splicing serves as a critical layer of gene expression regulation. Here, authors introduce SCASL for investigating the heterogeneity of RNA splicing landscapes at single-cell resolution, offering a novel scheme for classifying cell identities with physiological relevance.

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.

Florian Heyd describes a paper that pointed towards alternative splicing as a driver of human cognitive abilities.

A decade ago, the first bioinformatics pipelines to detect circular RNA molecules based on short-read sequencing data were published. Here, we show that dozens of such circular RNA detection tools differ vastly in their sensitivity but not in their specificity.

A new study in Science reports the mechanism through which TDP-43 enables correct processing of STMN2 mRNA, and proposes strategies to restore neuronal Stathmin-2 synthesis in TDP-43 proteinopathies.

In this comment, the authors discuss the potentially widespread problem of selection bias in drawing biological conclusions from RNA sequencing data.