mRNA 3′ UTRs chaperone intrinsically disordered regions to control protein activity

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.

cell.com

mRNA 3′ UTRs chaperone intrinsically disordered regions to control protein activity

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.

cell.com

When membrane insertion sets the pace of mitochondrial translation

Nature Structural & Molecular Biology, Published online: 07 May 2026; doi:10.1038/s41594-026-01799-3Human mitochondrial ribosomes synthesize membrane proteins while docked at the inner membrane, but how insertion feeds back onto decoding has remained unclear. A recent study reveals that nascent-chain topology and early folding within the mitoribosomal vestibule modulate elongation speed, establishing kinetic checkpoints during respiratory chain biogenesis.

dlvr.it

Membrane insertion of mitochondrial-encoded proteins regulates ribosome decoding speed

Nature Structural & Molecular Biology, Published online: 07 May 2026; doi:10.1038/s41594-026-01803-wSchöndorf and Petrychenko et al. show that mitochondrial translation speed is coupled to OXA1L-mediated inner membrane insertion, with cotranslational nascent chain folding and insertion driving structural changes and translational pausing.

dlvr.it

Single-molecule dynamics of the TRiC chaperonin system in vivo - Nature

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.

go.nature.com

CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis

CRISPR screens in iPSC-derived neurons reveal that the E3 ubiquitin ligase CRL5SOCS4 ubiquitinates tau, that CUL5 expression is correlated with resilience in human Alzheimer’s disease, and that electr...

cell.com

The ribosome synchronizes folding and assembly to promote oligomeric protein biogenesis

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...

cell.com

GroEL/ES chaperonin unfolds then encapsulates a nascent protein on the ribosome - Nature Communications

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...

nature.com

Proteotoxic stress response drives T cell exhaustion and immune evasion - Nature

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.

nature.com

The human ribosome modulates multidomain protein biogenesis by delaying cotranslational domain docking - Nature Structural & Molecular Biology

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...

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Lysosomal RNA profiling reveals targeting of specific types of RNAs for degradation

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...

biorxiv.org

A split-site E3 ligase mechanism enables ZNFX1 to ubiquitinate and cluster single-stranded RNA into ubiquitin-coated nucleoprotein particles

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 ...

cell.com

A conserved mechanism for the retrieval of polyubiquitinated proteins from cilia

CFAP36, a conserved cilia-specific ubiquitin reader, partners with the ARL3 GTPase to enable the selective and directional retrieval of polyubiquitinated proteins from cilia, a process essential for m...

cell.com

Complex II assembly drives metabolic adaptation to OXPHOS dysfunction

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

science.org

Structural analyses define the molecular basis of clusterin chaperone function

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...

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mRNA 3′UTRs chaperone intrinsically disordered regions to control protein activity

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

biorxiv.org

Probing condensate microenvironments with a micropeptide killswitch - Nature

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

nature.com

HCR-Proxy resolves site-specific proximal RNA proteomes at subcompartmental nanoscale resolution

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...

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Translational activity of 80S monosomes varies dramatically across different tissues

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

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The nascent polypeptide-associated complex (NAC) as regulatory hub on ribosomes

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...

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