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Two recent cryo-EM structures of the human L-type heteromeric amino acid transporter LAT1–CD98hc reveal surprising new insights into both amino acid transport in the human body and the roles of CD98hc as a cell-surface antigen and trafficking chaperone.
Epigenetic memory of silent chromatin often requires robust feedback loops between factors processing small non-coding RNAs and enzymes involved in heterochromatin assembly. A study published in Molecular Cell now demonstrates that these feedback loops can persist in a phenotypically neutral state even when gene expression is reactivated, and that they maintain the potential to reinstall heterochromatin in later generations when conditions change.
Cytosine methylation (m5C) is one of the more disputed base modifications of the epitranscriptome, mostly because current methods for detection are prone to artifacts. A new approach to increase detection accuracy reveals intriguing evidence of a role for the tRNA methyltransferase NSUN2 in the methylation of mRNA.
In the ribosome-associated quality control (RQC) pathway, stalled ribosomes are ubiquitinated and dissociated into subunits. The nascent protein chain associated with the 60S ribosomal subunit is ubiquitinated by the E3 ligase Listerin (Ltn1) and is released from tRNA by ANKZF1 (Vms1) for proteasomal degradation. Shao and colleagues now report that ANKZF1 (Vms1)-cleaved tRNAs are recycled via a two-step process that requires the removal of a terminal 2′,3′-cyclic phosphate and the addition of CCA by TRNT1.
Ribonucleotides that are misincorporated into DNA during replication are removed by topoisomerase 1, which generates 3′-terminal adducts that are not amenable to DNA repair and thus compromise genome stability. A recent report by Li et al. reveals that Apn2/APE2 resolves such blocked 3′ termini, thereby suppressing topoisomerase 1–induced mutations at ribonucleotide monophosphate sites within the genome.
RNAs perform diverse cellular functions that are mediated at least in part by their structure. However, how RNA structure changes throughout the RNA lifecycle and how these changes affect RNA function remain incompletely understood. A detailed in vivo characterization of RNA structure in various cellular subcompartments now provides insights into how RNA structural changes influence translation, RNA decay, protein binding and RNA modification.
Intertwining of DNA molecules frequently results in the formation of ‘ultrafine bridges’ between sister chromatids that need to be resolved during segregation of the chromatids into daughter cells. Although it has been established that these DNA bridges are coated by the helicase PICH, it has remained unknown how PICH assists in their resolution. A study now reveals that PICH directs the formation of positive DNA supercoiling in the presence of type I topoisomerases to promote the subsequent disentanglement of these DNA helices by type II topoisomerases. Remarkably, PICH might be able to reconfigure DNA topology by extruding loops of DNA while it moves along the double helix.
Chromatin organization in the nucleus plays an important role in cell-type-specific gene expression. A new study reports reconstruction of the 3D genome in single sensory neurons and provides insights into the regulation of genes encoding odorant receptors.
Bacteriophage-encoded anti-CRISPR (Acr) proteins were previously thought to inhibit CRISPR-mediated immunity by acting as physical barriers against the binding or cleavage of DNA. Two new studies report that recently discovered type V Acr proteins use enzymatic activities to shut down the Cas12a endonuclease, providing a multi-turnover ‘off switch’ for CRISPR-based immunity and technology.
Ubiquitin and ubiquitin-like proteins (UBLs) are essential regulators of a multitude of cellular processes, including autophagy. It is known that these proteins relay their effects by covalently modifying their substrate molecules. As an exception to this norm, Pang et al. report a novel phenomenon in which the UBL ATG12 interacts with its substrate ATG5 in a non-covalent fashion to promote autophagy in apicomplexan parasites and some yeasts.
Last year, several studies reported that proteins form biomolecular condensates at gene enhancers. Nair et al. now show that these condensates undergo physical changes over time, which affects their nuclear localization and the transcriptional output of their target genes.
Autophagy is a highly contextual modulator of tumorigenesis. A new study shows that autophagy can serve as a tumor suppressor to mediate cell death at replicative crisis.
Structural information on the respiratory supercomplex III2IV2 from budding yeast and from Mycobacterium smegmatis has become available, with cryo-EM work from four different groups.
A growing body of evidence suggests that cotranslational folding occurs from bacteria to mammalian cells, in particular for multi-domain proteins. In the assembly of yeast proteasomes, the initial interaction of Rpt1 and Rpt2 subunits has been found to take place on the translating ribosomes, coordinated by elongation pausing and involving the formation of Not1-containing compartments.
