Splicing of pre-mRNA requires both high fidelity and enormous sequence flexibility, inevitably resulting in aberrant, stalled complexes that must be discarded. A study now describes cryo-EM structures of stalled complexes poised for disassembly, determining aspects of aberrant complex recognition and splicing quality control.

We identify that signal-dependent and ligand-dependent enhancer activation programs require release of a shared enhancer RNA (eRNA) transcription checkpoint. Further mechanistic evidence reveals signal-dependent activation of P-TEFb on enhancers, which licenses the enhancer transcriptional program by overcoming pausing of transcription and promoting eRNA elongation.

Disruption of the enzyme O-GlcNAc transferase in mouse embryonic stem cells unleashes the activity of TET enzymes, which cause genome-wide decreases in DNA methylation and increases in DNA hydroxymethylation. This leads to de-repression of transposable elements, as well as the activation of some nearby genes.

The E. coli chaperonin GroEL forms nano-cages for protein folding. Bacterial chaperonin paralogues exhibit divergence at their C-terminus. Here, the authors demonstrate that the Gly-Met-rich C-termini are functionally significant in protein folding.

Focal cortical dysplasia type II causes epileptic seizures and is associated with various types of neuronal abnormalities. This study uses patient tissue transcriptomics and animal models to reveal that vascular malformations are a key part of the pathology by creating ischemic-hypoxic microenvironments.

The molecular etiology of hypertensive disorders of pregnancy is largely unknown. Here the authors show from a prospective study of diverse pregnancies that the disease can be split into molecular subtypes based on RNA data and validated a classifier for individuals with no preexisting high risk factors.

Rixosome has critical roles in ribosome biogenesis and silencing of Polycomb target genes. Here authors Huang and Tong report the structures of several sub-complexes of rixosome and a model for the core scaffold of this complex.

Arrayed and pooled high-throughput screening is crucial for drug discovery and CRISPR functional genomics. Here, the authors present dFLASH; a dual FLuorescent transcription factor Activity Sensor for Histone-integrated live-cell reporting for high performance screening applications across numerous pathways and screening contexts.

Cancer cells rely on mitochondria for energy and macromolecule synthesis. Here, the authors show that RNA G-quadruplex dynamics, driven by oncogenic signals, regulate the translation of nuclear-encoded mitochondrial mRNAs, affecting mitochondrial function and promoting cancer cell growth.

Splicing of pre-mRNA requires both high fidelity and enormous sequence flexibility, inevitably resulting in aberrant, stalled complexes that must be discarded. A study now describes cryo-EM structures of stalled complexes poised for disassembly, determining aspects of aberrant complex recognition and splicing quality control.

This study shows that zotatifin selectively inhibits the translation of prostate cancer oncogene transcripts by restructuring their 5′ untranslated regions. In mice, this agent reversed treatment resistance, which led to improved survival.

We identify that signal-dependent and ligand-dependent enhancer activation programs require release of a shared enhancer RNA (eRNA) transcription checkpoint. Further mechanistic evidence reveals signal-dependent activation of P-TEFb on enhancers, which licenses the enhancer transcriptional program by overcoming pausing of transcription and promoting eRNA elongation.

Disruption of the enzyme O-GlcNAc transferase in mouse embryonic stem cells unleashes the activity of TET enzymes, which cause genome-wide decreases in DNA methylation and increases in DNA hydroxymethylation. This leads to de-repression of transposable elements, as well as the activation of some nearby genes.

Gene expression analyses and functional studies reveal that the salivary glands of mosquitoes have rhythmic genes, including those involved in bloodmeal digestion. In addition, the malaria parasite’s sporozoites show daily rhythms, which suggests that synchronized clocks among mosquitoes, parasites and the host enhance transmission efficiency.