A proteotoxic stress response specific to exhausted T cells, governed by AKT signaling and accompanied by increased protein translation, represents a mechanistic vulnerability and a new therapeutic target to improve cancer immunotherapies.

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...

Autophagy targets a wide variety of substrates for degradation within lysosomes. While lysosomes are known to possess RNase activity, the role of lysosomal RNA degradation in post-transcriptional gene...

Grabarczyk et al. show the structure and mechanism of a non-canonical ubiquitin ligase, which is activated through nucleic-acid-induced oligomerization and is critical for cell survival during immune ...

Succinate dehydrogenase assembly dynamics maintains metabolic homeostasis during mitochondrial oxidative stress.

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

Targeting a non-natural micropeptide ‘killswitch’ to several biomolecular condensates altered condensate compositions and revealed condensate functions in human cells

The spatial organisation of RNA condensates is fundamental for understanding of basic cellular functions, but may also provide pivotal insights into diseases. One of the major challenges to understand...

Abstract. Translational regulation at the stage of initiation can impact the number of ribosomes translating each mRNA molecule. However, the translational

The correct synthesis of new proteins is essential for maintaining a functional proteome and cell viability. This process is tightly regulated, with ribosomes and associated protein biogenesis factors...

Millions of ribosomes are packed within mammalian cells, yet we lack tools to visualize them in toto and characterize their subcellular composition. In this study, we present ribosome expansion micros...

The accumulation of protein aggregates has been causatively linked to the pathogenesis of neurodegenerative diseases. In this study, we have conducted a genome-wide CRISPR-Cas9 screen to identify cell...

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

Ribosomes cooperate through transient collisions to ensure efficient translation.

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

Nearly all mitochondrial proteins are imported into mitochondria from the cytosol. How nascent mitochondrial precursors acquire and sustain import-competence in the cytosol under normal and stress con...

Salary for this Role: From £43,210 with benefits, subject to skills and experience Job Title: Postdoctoral Fellow - Balchin Lab Reports to: David Balchin Closing Date: 28/Feb/2025 23.59 GMT Job Descri...