How do cells ensure that complex, multidomain proteins fold correctly? Luo et al. reveal a self-contained solution. The 3′UTR of an mRNA co-translationally chaperones the protein it encodes, preventin...

Highly conserved mRNA 3′ UTRs act as co-translational chaperones for intrinsically disordered regions (IDRs), preventing inter-domain misfolding and enabling biogenesis of fully active proteins.

Aberrant aggregation of the prion-like RNA binding protein TDP-43 drives several fatal neurodegenerative proteinopathies, including amyotrophic lateral sclerosis (ALS). In this work, we define how sho...

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Instructions in preprints from 14 universities highlight controversy on AI in peer review

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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

Genetically modified E coli used to create painkillers from material produced from plastic bottles

Subcellular RNA organization can affect critical cellular functions. However, our understanding of RNA microenvironments, particularly biomolecular condensates, remains limited, largely due to a lack ...

Schärfen et al. develop a method to measure the structure of nascent RNAs during their synthesis by RNA polymerases. Base pairing occurs rapidly in cells, revealing the strong regulatory potential of ...

I shared a controversial take the other day at an event and I decided to write it down in a longer format: I’m afraid AI won't give us a compressed 21st century.

Cells constantly surveil and monitor their proteome to ensure proper function. These processes, spanning multiple steps from protein synthesis to folding and degradation, are collectively known as pr…

The localization of biomolecular condensates to intracellular membrane surfaces has emerged as an important feature of sub-cellular organization. In this work,

Single-molecule live-cell fluorescence in situ hybridization uses an RNA-targeting CRISPR–Csm complex to image and track endogenous RNAs.

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Boraas et al. identify that mRNAs and the stress granule RNA-binding protein G3BP1 form ribonucleoprotein (RNP) complexes at FAs. These RNPs regulate FA protein mobility and cell migration under norma...

Biomolecular condensates play key roles in the spatiotemporal regulation of cellular processes. Yet, the relationship between atomic features and condensate function remains poorly understood. We stud...

Using a deep neural network and statistical analyses of atomic force microscopy images of individual RNA molecules enables the mapping of RNA conformational space in solution.

Improved effectors for CRISPRi/CRISPRa are developed following high-throughput screening of transcriptional domains.

PEER-seq characterizes the drug resistance profiles of thousands of genetic variants.

Ribozymes are small catalytic RNA sequences capable of nucleotide-specific self-cleavage found widespread in nature. Ribozyme cleavage generates distinct 2′,3′-phosphate and 5′-hydroxyl termini that r...

The ambitious goal of the new Brown RNA Center is to untangle the mysteries of human RNA, which could be instrumental in preventing and developing treatments for a wide variety of complex diseases.

Like all canonical PUF proteins, C. elegans FBF-2 binds to specific RNAs via tripartite recognition motifs (TRMs). Here we report that an FBF-2 mutant protein that cannot bind to RNA, is nonetheless b...