Reviews & Analysis

The ribosome-associated complex (RAC) is formed by the JD protein Zuo1 and the unconventional Hsp70 Ssz1. This Review presents recent developments that have increased our understanding of RAC's mechanisms and cellular functions.

Long noncoding (lnc)RNAs are postulated to control diverse biological processes by modulating transcription, yet for most lncRNAs evidence supporting this function has been lacking. A new report describes the role of a novel class of lncRNAs—chromatin-associated enhancer RNAs or cheRNAs—in the regulation of proximal gene expression.

The envelope glycoprotein spike, the sole antigen on the Lassa virus (LASV) surface, constitutes the focal point of the host neutralizing immune response. A high-resolution structure of the trimeric LASV glycoprotein in an antibody-bound form illuminates the molecular architecture of the antigen and reveals the mode of action of the most abundant known class of Lassa-specific human neutralizing antibodies.

Cytoplasmic dyneins transport cellular components from the periphery toward the center of the cell. By moving cargoes along microtubules, dyneins ensure proper cell division, regulate exchange of materials between organelles, and contribute to the internal organization of eukaryotic cells. Two recent studies show that, upon dimerization, cytoplasmic dyneins intrinsically adopt an autoinhibited configuration that can be relieved by other factors to precisely control motor activity and regulate dynein-based transport.

Two new studies show that RNA-binding proteins can mediate distinct and beneficial effects to cells by binding to the extensive double-stranded RNA (dsRNA) structures of inverted-repeat Alu elements (IRAlus). One study reports stress-induced export of the 110-kDa isoform of the adenosine deaminase acting on RNA 1 protein (ADAR1p110) to the cytoplasm, where it binds IRAlus so as to protect many mRNAs encoding anti-apoptotic proteins from degradation. The other study demonstrates that binding of the nuclear helicase DHX9 to IRAlus embedded within RNAs minimizes defects in RNA processing.

Interaction with heterotrimeric G proteins is a hallmark of G-protein-coupled receptor (GPCR) family members, and it is the key step for a diverse range of cell-signaling cascades. A recent cryo-EM structure of the human calcitonin receptor (CTR) in complex with a G-protein heterotrimer reveals novel insights into receptor–G-protein coupling.

Chromatin remodelers are ATP-driven enzymes that can slide nucleosomes along DNA. Chen and colleagues present a tantalizing ∼4-Å view of the SWI/SNF ATPase motor bound to the nucleosome, which offers novel structural clues into the remodeling process.

The spatial organization of the genome profoundly influences how genes are regulated in normal development or dysregulated in disease. A new study of the murine HoxB locus illustrates how promoter interactions direct higher-order chromatin folding.

The number of conferences on epigenetics has been increasing in the past decade, underscoring the impact of the field on a variety of areas in biology and medicine. However, the mechanistic role of the epigenome in adaptation and inheritance, and how the environment may impinge on epigenetic control, are topics of growing debate. Those themes were the focus of the inaugural international King Abdullah University of Science and Technology (KAUST) Research Conference on Environmental Epigenetics in Saudi Arabia, where more than 100 participants from 19 countries enjoyed vibrant scientific discussions and a pleasant February breeze from the Red Sea.

The DNA-adenine modification 6mA has recently been identified in metazoans. This Perspective summarizes the latest discoveries and suggests potential functional roles for 6mA in metazoan genomes.

O-GlcNAc is a reversible post-translational modification that is added by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). OGA is emerging as a therapeutic target for multiple diseases, but its structure has been elusive until now.

One of the striking features of cells seen through a microscope is the heterogeneous organization of the nuclei. A combination of molecular methods and computational modeling has now been used to reconstruct accurate 3D structures of the genome inside single nuclei.

As cells undergo terminal differentiation, the composition of Polycomb-repressive complex 2 (PRC2) changes and the histone H3K27 methyltransferase Ezh2 is progressively replaced by its homolog Ezh1. By identifying an enzymatically inactive splice variant of Ezh1 that is sensitive to cellular stress, Bodega et al. now demonstrate that PRC2–Ezh1 has an essential role in establishing an altered gene expression program required for postmitotic muscle cells to adapt to environmental changes.

In this Perspective, the authors consider how DNA breaks stimulate R-loop formation, particularly within actively transcribed genomic regions, and discuss the cellular mechanisms that prevent or remove RNA–DNA hybrids to preserve genome integrity.

Chromatin-remodeling enzymes perform the formidable task of reorganizing the structure of a stable macromolecular assembly, the nucleosome. Recently published work demonstrates that the SNF2H chromatin remodeler distorts the histone octamer structure upon binding to the nucleosome, then taps into this induced plasticity to productively achieve nucleosome sliding.

The binding of foreign peptides to host major histocompatibility complex (MHC) forms the basis of adaptive immune recognition. The MHC and T cell receptors (TCRs) use diverse structural solutions to enhance peptide presentation and recognition, and two new reports provide insights into noncanonical modes of detection and binding.

Separases are crucial cell cycle proteases that control the metaphase-to-anaphase transition by cleaving chromosomal cohesin rings. Two new high-resolution structures of separase bound by its inhibitory chaperone securin illustrate intriguing regulatory mechanisms.

Unlike in animals in which gastrulation marks the onset of zygotic transcription and a transition from random to site-specific localization of replication origins, transcription and origin specification in Caenorhabditis elegans are in place before gastrulation. Nonetheless, origin-site redistribution takes place after gastrulation, and is coordinated with changes in the sites of active transcription.

This Review highlights recent breakthroughs in X-chromosome inactivation and discusses how the multitasking RNA Xist can structurally and functionally transform an active chromosome into uniquely organized facultative heterochromatin.