Volume 29 Issue 12, December 2022

In this Perspective the authors discuss the major challenges when studying the role of enhancers in disease etiology, highlighting a path forward for future studies aiming to understand the molecular basis of enhanceropathies.

Rengachari et al. provide a structural investigation of Pol II initiation at snRNA gene promoters and find that the snRNA-activating protein complex enables DNA opening and transcription initiation independent of TFIIE and TFIIH in vitro.

This work provides molecular insights into the export of cyclic glucans by a bacterial ABC transporter. The findings expand our understanding of polysaccharide trafficking across bacterial membranes, as well as protein-sugar interactions in general.

Basu and colleagues comprehensively characterize how sequence and epigenetic modifications impact the local mechanical properties of DNA. The results suggest that DNA mechanics may have evolved to aid diverse DNA-deforming biological processes.

Cryo-EM has facilitated structural studies of membrane proteins, but inactive GPCRs have remained inaccessible due to their small size. Robertson et al. demonstrate a common nanobody-based approach to streamline the determination of such structures.

LRRK2 is one of the most commonly mutated genes in familial Parkinson’s disease. Here, the authors report a cryo-EM structure of the catalytic half of LRRK2 bound to microtubules, revealing determinants of binding that are independent of LRRK2 kinase activity.

The voltage-gated sodium channel Na_V1.7 plays essential roles in pain sensation. The authors report cryo-EM structures of Na_V1.7 in complexes with three pore blockers, elucidating distinct mechanisms of action of their modulation on Na_V1.7.

Hall et al. discovered the molecular mechanism for the polarity of the CRISPR roadblock to transcription: RNA polymerase progression can collapse the R-loop formed by a bound dCas to allow read-through from the PAM-distal side. Guide RNA modifications allow modulation of the dCas R-loop stability.

Cruz et al. present cryo-EM structures of large ribosomal subunit assembly intermediates that reveal how the DEAD-box helicase Spb4 remodels rRNA secondary structures to facilitate and guide 60S maturation.

The authors describe how three types of cis-element (CTCF sites, active TSSs and TTSs) regulate cohesin trafficking along chromosomes. They uncover that this cohesin traffic pattern is genetically linked to gene regulation and RNA processing.

Here the authors show that DNMT3A and DNMT3B are differentially regulated during endoderm and mesoderm differentiation in mouse development and characterize the dynamic DNMT3A and DNMT3B sequence specificity during gastrulation.

ABC-type heterotrimeric proteins can be designed de novo using coiled coils and helical bundles as starting scaffolds, extended using helical repeat proteins and then used as building blocks for higher-order oligomeric assemblies.

The authors perform parallel transcriptome sequencing, tRNA qPCR array, ribosome profiling and mass spectrometry across five stages of mouse neocortex development to model the dynamic transcriptome-to-proteome transition, discovering a critical prenatal window during which translational control is predominant.