Perspectives

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.

Recent structures of eukaryotic membrane protein insertases of the Oxa1 superfamily reveal a conserved protein module and common mechanistic principles that enable membrane insertion of a diverse set of substrates.

Emerging evidence that telomere-specific Shelterin components also play roles in DNA replication timing within heterochromatin and genome maintenance suggests a potential common evolutionary origin of their protective and regulatory functions.

Tzelepis, Rausch and Kouzarides review the action of RNA modifications in the context of chromatin and discuss the emerging potential of RNA-modifying enzymes as new drug targets.

Arrowsmith and Schapira review recent progress in the discovery of drug-like small molecules that antagonize the function of non-bromodomain chromatin readers.

Noberini and Bonaldi discuss how mass spectrometry–based technologies aid in identifying the full target spectrum of bioactive molecules.

James Kadonaga provides a retrospective of the biochemical analyses that demonstrated the role of chromatin in the regulation of RNA polymerase II transcription.

This personal Perspective by Joan and Ron Conaway describes the biochemical identification and characterization of three key transcription elongation factors, TFIIS, Elongin and ELL, and summarizes how the delineation of their functions has informed the understanding of the regulatory mechanisms that control elongation by RNA polymerase II.

This historical Perspective by John Lis summarizes the array of complementary biochemical, genetic, optical and genome-wide approaches that have enabled dissection of eukaryotic transcriptional mechanisms in their native, cellular environment, and considers the future insights offered by emerging technologies of ever-increasing sensitivity and resolution.

Diederichs and colleagues review RNA motifs, focusing on four recent studies identifying nuclear-retention motifs, and discuss the limited specificity of short RNA motifs and the resulting challenge for effective functional prediction.

Nichols and Corces summarize the current knowledge of SMC structure and function and propose a new mechanism for SMC motor activity, which is central to the DNA loop extrusion model of genome organization.

Rittinger and Walden review recent structural and functional insights to contrast and compare RBR E3 ubiquitin ligases and their regulation through autoinhibition, post-translational modifications, multimerization and protein-protein interactions.

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.

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.

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.

This Perspective focuses on five distinct regulatory elements that have been recognized as being critical for generating and modulating oscillatory dynamics in time and space, in both natural and synthetic biological networks.

This Perspective provides an overview of the major advances in recent years in the computational design and structure prediction of α-helical membrane proteins.

The use of nanodiscs is substantially fostering structural and functional studies of membrane protein. This Perspective summarizes the recent use of nanodiscs as an invaluable tool for the characterization of membrane proteins.

This Perspective provides an overview of recent progress, successes, challenges and future opportunities in the application of solution NMR and solid-state NMR methods to study the structure, dynamics and function of membrane proteins.

This Perspective discusses how two complementary approaches, bottom-up in vitro and top-down in situ structural biology, have now converged to generate the first predictive structural models of the nuclear pore scaffold.