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Deadenylation of mRNAs is generally associated with translational inhibition and mRNA decay. A study now reports that, unexpectedly, highly expressed genes tend to have shorter poly(A) tails and suggests that poly(A) tails can be 'pruned', generating a 30-nucleotide-biased phased distribution, likely due to protection by poly(A)-binding proteins.
The helicase intrinsic to DNA polymerase θ (Polθ), the versatile mediator of microhomology-based repair of DNA double-strand breaks and stalled replication forks, is now revealed to be a member of an elite group of proteins known as annealing helicases. This small family of enzymes remodels DNA intermediates in multiple repair processes that are crucial to preserving genome stability and warding off cancer and aging.
The crystal structure of an oligosaccharyltransferase in complex with a sugar donor and an acceptor peptide provides insight into the mechanism of protein glycosylation and reveals how lipid-linked oligosaccharides are positioned in the enzyme active site.
The mechanics and mechanisms of ribosomal translocation, including the conformational rearrangements in the ribosome and the roles of EF-G and tRNAs, are discussed in this Perspective by Mohan, Noller and colleagues.
In this Review, the authors consider how single-molecule biophysical approaches can inform our understanding of the ring-shaped structural maintenance of chromosome (SMC) complexes and their function in chromosome organization.
Assembly of the small ribosomal subunit from an RNA strand and 33 proteins is an intricate and dynamic process. Two cryo-EM studies now provide insight into a complicated complex of at least 51 trans-factors that act on the preribosomal small subunit to sequentially fold it into a 3D molecular machine.
This review highlights recent mechanistic insights into the CRISPR class 2 type V enzymes Cpf1 and C2c1, which are crucial for improving these genome engineering tools and expanding the genomic editing space.
PCSK9 enhances LDL cholesterol (LDL-c) levels by escorting the liver LDL receptor (LDLR) to endosomes and lysosomes for degradation. PCSK9 monoclonal antibodies and RNA-antisense formulations are effective in reducing LDL cholesterol in patients. The recent structural identification of a novel pocket in PCSK9 paves the way to the future development of orally active small-molecule hypocholesterolemic drugs.
The cellular crosstalk between different classes of regulatory noncoding RNAs has reached a new spatial dimension. Jiang et al. reveal an essential role of a nuclear-paraspeckle-organizing long noncoding RNA and its protein partners in regulating the first steps of microRNA biogenesis.
C-type inactivation is a process by which ion flux through a voltage-gated K+ channel is regulated at the selectivity filter. A recent structure of the Kv1.2 channel provides a view into the structural changes of the selectivity filter during C-type inactivation.
PERK is a major sensor of the unfolded protein response controlling cell fate under endoplasmic reticulum (ER) stress. A new study reveals an additional step for optimal PERK signaling, involving the binding of CNPY2 to PERK's luminal domain. The PERK–CNPY2 axis was shown to enhance cell death under ER stress in vivo influence liver disease.
Five protein complexes, CI–CV, form the oxidative phosphorylation electron transport chain in the mitochondrial membrane and can be found organized into supercomplexes (SCs): I+III2+IV, or respirasome; I+III2; III2+IV; and CV2. Letts and Sazanov review current knowledge on the structure, assembly and function of respiratory SCs.
The robustness of the circadian clock deteriorates with aging. Two new studies show that aging reprograms the circadian transcriptome in a cell-type-dependent manner and that such rewiring can be reversed by caloric restriction.
Group II chaperonins facilitate protein folding by undergoing ATP-driven conformational changes. A recent study reveals a tunable allosteric network in group II chaperonins that includes a residue at the intersubunit interface, which is important for assembly and allosteric coordination. The authors also propose that lower cooperativity allows group II chaperonins to achieve optimal substrate folding over a broad range of ATP concentrations.
The monoallelic expression of many imprinted genes in mammals depends on DNA methylation marks that originate from the germ cells. Recent studies in mice and fruit flies evoke a novel, transient mode of genomic imprinting in which oocyte-acquired histone H3 Lys27 trimethylation (H3K27me3) marks are transmitted to the zygote and modulate the allele specificity and timing of gene expression in the early embryo.
In this Review, Peña, Hurt and Panse discuss our current knowledge on the eukaryotic ribosome assembly, a complex process that takes place across different cellular compartments and involves over 200 assembly factors.
Meiotic progression is controlled by cytoplasmic polyadenylation and translational activation of masked, maternal mRNAs. RNA-binding-protein interactions with adjacent cis elements cause local conformational changes to the mRNAs that determine the extent and timing of their activation.
An unusual pairing of homologous X chromosomes occurs during X inactivation. A new study in mouse embryonic stem cells shows that telomeres and the telomeric RNA PAR-TERRA are responsible for additional pairwise interactions that guide Xic–Xic pairing.
