Volume 24 Issue 6, June 2017

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.

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.

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.

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.

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.

The human enzyme CTP synthase forms polymeric filaments with increased catalytic activity, in contrast to the inactive filaments formed by bacterial CTP synthase. Cryo-EM and crystallographic analyses explain the structural bases for those different behaviors.

Homotypic interactions between active and Polycomb-repressed promoters co-occurring in the same DNA fiber, rather than CTCF occupancy, explain the 3D HoxB folding pattern.

A working model for β-cardiac myosin in the sequestered state and binding assays reveal interactions between the myosin head and tail that are disrupted by mutations associated with hypertrophic cardiomyopathy.

In stressed cells, the ADAR1p110 isoform is phosphorylated and translocated from the nucleus to the cytoplasm, where it protects transcripts with 3′-UTR dsRNA structures from Staufen1-mediated decay, thus suppressing cellular apoptosis.

X-ray crystallography and NMR analysis demonstrate that, contrary to previous observations, ^fC does not significantly alter DNA structure, thus suggesting an alternative basis for recognition of ^fC-DNA by epigenome-modifying enzymes.