Using SCN2A haploinsufficiency as a proof-of-concept, upregulation of the existing functional gene copy through CRISPR activation was able to rescue neurological-associated phenotypes in Scn2a haploin...

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

AbstractBackground. Authenticated preclinical brain tumor models provide unprecedented opportunities to evaluate next-generation treatments. However, some

The authors discover a homeostatic process termed interstasis, in which an increased concentration of proteins within RNA–protein condensates induces the sequestration of their own mRNAs.

One of the most devastating diseases finally has a treatment that can slow its progression and transform lives, tearful doctors tell BBC.

UPF1 depletion inhibits nonsense-mediated mRNA decay (NMD) and stabilizes direct target transcripts within hours. Boehm et al. use conditional protein degradation and advanced transcriptomics to map t...

Variants in spliceosomal small nuclear RNA (snRNA) genes RNU4-2 (ReNU syndrome), RNU5B-1 , and RNU2-2 have recently been linked to dominant neurodevelopmental disorders (NDDs), revealing a major, prev...

During organogenesis, precise pre-mRNA splicing is essential to assemble tissue architecture. Many developmentally essential exons bear weak 5'splice sites (5'SS) yet are spliced with high precision, ...

The cytokine messenger proteins known as interferons are central to protective immune responses against infections, but they are also involved in inflammatory and autoimmune diseases. This review maps...

Direct RNA-seq in brain reveals RNA isoform and region-specific m6A modifications, highlighting their role in gene regulation.

Mouse models show that respiratory infections from viruses such as influenza and SARS-CoV-2 can trigger metastasis of dormant breast cancer cells in the lungs, a finding supported by epidemiological d...

Nature Communications - The RNA editing enzyme ADAR1 blocks interferon responses triggered by cytosolic RNA sensors, and has been proposed as a potential target in immuno-oncology. Here, the...

Massively parallel reporter assays (MPRAs) are powerful technologies for measuring the impact of non-coding sequences on gene expression. Here, the authors demonstrate that MPRA reporters often underg...

RNA-binding motifs in eukaryotic proteins are presented in a comprehensive resource.

SPIDR, a massively multiplexed method that simultaneously maps dozens of RNA-binding proteins to their RNA targets at single-nucleotide resolution, uncovers new RNA-protein interactions and provides c...

More than 2,700 human mRNA 3′UTRs have hundreds of highly conserved (HC) nucleotides, but their biological roles are unclear. Here, we show that mRNAs with HC 3′UTRs mostly encode proteins with long intrinsically disordered regions (IDRs), including MYC, UTX, and JMJD3. These proteins are only fully active when translated from mRNA templates that include their 3′UTRs, raising the possibility of functional interactions between 3′UTRs and IDRs. Rather than affecting protein abundance or localization, we find that HC 3′UTRs control transcriptional or histone demethylase activity through co-translationally determined protein oligomerization states that are kinetically stable. 3′UTR-dependent changes in protein folding require mRNA-IDR interactions, suggesting that mRNAs act as IDR chaperones. These mRNAs are multivalent, a biophysical RNA feature that enables their translation in network-like condensates, which provide favorable folding environments for proteins with long IDRs. These data indicate that the coding sequence is insufficient for the biogenesis of biologically active conformations of IDR-containing proteins and that RNA can catalyze protein folding. ### Competing Interest Statement The authors have declared no competing interest. Pershing Square Foundation, https://ror.org/04tce9s05 G. Harold & Leila Y. Mathers Foundation National Institutes of Health, DP1GM123454, R35GM144046 Memorial Sloan Kettering Cancer Center, https://ror.org/02yrq0923, P30 CA008748