The human genome encodes several hundreds of ubiquitin E3 enzymes, most of which have poorly understood biological roles. In search for novel ubiquitin E3 enzymes involved in DNA damage tolerance, we ...

Formation of neuronal tau protein aggregates is a defining feature of tauopathies, including Alzheimer’s disease and frontotemporal dementia. Tau pathology propagates across brain regions by a cell-to...

Single-particle tracking experiments in intact cells reveal dynamic co- and post-translational interactions of the TRiC–PFD chaperonin complex with client proteins during in vivo protein folding.

Large oligomeric proteins constitute a major fraction of proteomes, but are difficult to refold in vitro, raising the question of how cells direct their biogenesis. Roeselová and Shivakumaraswamy et a...

The kinase ZAK is activated at collided ribosomes to mediate the ribotoxic stress response.

The GroEL/ES chaperonin can act during protein synthesis to promote folding. Here, Roeselová et al. show how GroEL captures, remodels and sequesters nascent proteins in its central chamber, while they...

During nutrient deprivation, activation of the protein kinase GCN2 regulates cell survival and metabolic homeostasis. In addition to amino acid stress, GCN2 is activated by a variety of cellular stres...

Eukaryotic genomes generate a plethora of polyadenylated (pA+) RNAs[1][1],[2][2], that are packaged into ribonucleoprotein particles (RNPs). To ensure faithful gene expression, functional pA+ RNPs, in...

By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding in...

Nature Structural & Molecular Biology - The authors reveal a three-domain architecture of glycoprotein clusterin and show that the hydrophobic tails are crucial for clusterin’s functions...

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

This study integrates ribosome profiling, single molecule methods and computational predictions to reveal that molecular chaperones bind ‘unsatisfied’ residues exposed on partial nascent folds, ration...

An ancient tRNA modification is used by mammalian cells to coordinate protein translation and adaptive signaling.

Abstract. Messenger RNA (mRNA) homeostasis is a critical aspect of cellular function, involving the dynamic interplay between transcription and decay proce

Ochre, a strain of Escherichia coli engineered to have a single stop codon, enables reassignment of four codons for non-degenerate functions, such as incorporation of non-standard amino acids into pro...

SCF–FBXO31 scans proteins for C-terminal amidation and marks them for subsequent proteasomal degradation.

We developed PRINT, a computational method that identifies footprints of DNA–protein interactions from bulk and single-cell chromatin accessibility data across multiple scales of protein size.

Zhou et al. discovered a specific role of adenosine modifications in the coding region of mRNAs. These chemical alterations slow down the movement of the ribosome during translation and trigger degradation of the corresponding mRNAs.

The eukaryotic signal recognition particle (SRP) cotranslationally recognizes the first hydrophobic segment of nascent secretory and membrane proteins and delivers them to a receptor at the endoplasmi...

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Zhou et al. discovered a specific role of adenosine modifications in the coding region of mRNAs. These chemical alterations slow down the movement of the ribosome during translation and trigger degrad...