A pre-rRNA positive feedback loop drives malignant ribosome biogenesis

Altered nucleoli are a well-established hallmark of cancer[1][1], but how oncogenic signalling remodels the nucleolus remains poorly understood. Here we used an inducible mouse model of pancreatic duc...

biorxiv.org

Structural basis for chaperone-guided assembly of RNA-induced silencing complex

Nature - Structures of the AGO maturation complex reveal how chaperones and an RNA duplex drive assembly of the RNA-induced silencing complex.

rdcu.be

Quantitative profiling of basal and stress-induced ribosome collisions

Ribosomes stall when they encounter problematic codons or cellular stress that perturbs translation. Stalled ribosomes can lead to the formation of ribosome collisions, also known as disomes, that eng...

biorxiv.org

Nascent chain folding status modulates ribosome dynamics and mRNA stability through the ribosome-associated chaperone Zuo1

Chang et al. show that co-translational protein misfolding feeds back to ribosomes, slowing translation elongation and triggering mRNA decay. The ribosome-associated chaperone Zuo1 mediates this respo...

cell.com

A pre-rRNA positive feedback loop drives malignant ribosome biogenesis

Altered nucleoli are a well-established hallmark of cancer[1][1], but how oncogenic signalling remodels the nucleolus remains poorly understood. Here we used an inducible mouse model of pancreatic duc...

biorxiv.org

Ribosome biogenesis bottlenecks reveal vulnerabilities in cancer

Cell growth requires elevated protein synthesis, which depends on the production of ribosomes. Ribosome biogenesis is a complex, multi-step pathway in which newly transcribed precursor ribosomal RNA (...

biorxiv.org

Structure and evolution-guided design of minimal RNA-guided nucleases

The design of RNA-guided nucleases with properties not limited by evolution can expand programmable genome-editing capabilities. However, generating diverse multidomain proteins with robust enzymatic ...

science.org

Molecular basis of polyadenylated RNA fate determination in the nucleus - Nature

Biochemical, structural and cell biological analyses reveal that UAP56 (DDX39B) assembles with a TREX-2–like module that redirects non-functional polyadenylated RNAs from export to degradati...

nature.com

Conformational diversity of collided ribosomes determines stress signaling

Translating ribosomes are stalled by amino acid starvation and by chemical damage of the mRNA template, leading to ribosome collisions. These collisions serve as signaling platforms that promote quali...

biorxiv.org

Mechanism of nucleolytic degradation of human ribosomes

Stresses like starvation trigger degradation of mature 40S ribosomes, requiring the coordinated breakdown of large and stable RNA-protein complexes. The atypical kinase RIOK3 orchestrates degradation ...

biorxiv.org

The atypical E3 ligase HOIL-1 safeguards the ribosome during cellular stress

Nature Cell Biology - Douglas et al. study the E3 ligase HOIL-1, mutated in patients with a type of myopathy. Mutant HOIL-1 influences the sensitivity to disulfidptosis initiated by...

rdcu.be

Evolution of a core ribosomal innovation in octopus

Much of biology focuses on how genetic changes mediate new functions, but less attention is given to adaptations in other steps of the central dogma. Octopuses exhibit complex nervous systems and soph...

biorxiv.org

Membrane protein solubilization and structure determination using de novo–designed proteins

Developing therapies and vaccines against integral membrane proteins is hindered by their extensive hydrophobic surfaces, which complicate production and structural analysis. Here, we describe a gener...

science.org

Alternate RNA decoding results in stable and abundant proteins in mammals

Nature - Alternate RNA decoding, an understudied process, leads to peptide sequence modifications that can have substantial functional effects on protein stability, tissue-specific proteomes and...

rdcu.be

Nucleoplasmic checkpoint of the 40S ribosomal decoding center maturation

Lau et al. report that Rrp12 coordinates ordered decoding center assembly during 40S biogenesis by promoting timely assembly factor release and preventing premature rRNA folding. Rrp12 C-terminal trun...

cell.com

Opinion | The Science That Turned Lizard Venom Into GLP-1s Is Under Attack

nytimes.com

RNF25 confers mRNA damage tolerance by curbing activation of the integrated stress response

Excessive RNA damage activates cellular stress responses, triggering cell death. However, pathways that negatively regulate RNA damage responses are l…

sciencedirect.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

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

Substrate selectivity of the human RNA m5C methyltransferase NSUN2 - Nature

NSUN2 is an enzyme that adds a small chemical mark to RNA molecules and uniquely selects its targets based on specific sequence patterns and structural features.

nature.com

Translation efficiency covariation identifies conserved coordination patterns across cell types

Nature Biotechnology - Matched ribosome profiling and RNA sequencing data quantify translation efficiency patterns across 140 human and mouse cell lines.

rdcu.be

A natural depsipeptide antibiotic binds the E-site of the bacterial ribosome

Nature - Improved fractionation strategies can identify antibiotics with previously unseen scaffolds and mechanisms, exemplified by manikomycin from Streptomyces rimosus, which acts by targeting...

rdcu.be

2′-O-Methylation maintains ribosome structural and translation integrity

By examining the translational properties and high-resolution structural features of yeast ribosomes lacking snoRNP-directed rRNA 2′-O-methylation, Zhao et al. demonstrated that 2′-O-methylation is es...

cell.com

Mechanism of RACK1-dependent ZAKα activation at stalled and collided ribosomes

The ribotoxic stress response is activated upon sensing of impaired translation by the MAP3 kinase ZAKα. Vind et al. demonstrate how ZAKα surveils the translation process and interacts with elongating, stalled, and collided ribosomes. ZAKα activation depends on ribosome-templated sequestration of inhibitory domains, dimerization, and activation-loop autophosphorylation in trans.

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The atypical E3 ligase HOIL-1 safeguards the ribosome during cellular stress | Nature Cell Biology

The ribosome has emerged as a signalling hub that can sense metabolic perturbations and coordinate responses that either restore homeostasis or initiate cell death. The range of insults that signal via the ribosome and the mechanisms governing such cell fate decisions remain uncharacterized. Here we identify the atypical E3 ligase HOIL-1 as an unexpected node in the ribosome signalling network that resolves cellular stress. We find that truncating HOIL-1 mutations associated with dilated cardiomyopathy exacerbate cardiac dysfunction in mice and broadly sensitize cells to nutrient and translational stress. These diverse signals converge on the MAP3K ZAKα, a sentinel of ribotoxic stress. Mechanistically, HOIL-1 promotes ribosome ubiquitination and facilitates cytoprotective ribosome-associated quality control. HOIL-1 loss of function causes glucose starvation to become ribotoxic, leading to ZAKα-dependent ATF4 activation and disulfidptosis driven by the cystine–glutamate antiporter xCT.

doi.org

Mechanisms and disease relevance of mitochondrial translation in humans

Nature Reviews Molecular Cell Biology - This Review discusses new insights into the intricate regulation of mitochondrial protein synthesis, the pathological consequences of its dysfunction in...

rdcu.be

mTOR-NAA10-C7orf50 axis senses nutritional status to coordinate ribosome biogenesis and autophagy

C7orf50 is a nutrient-responding nucleolar factor that coordinates ribosome biogenesis and autophagy.

science.org