Perspectives

This Perspective discusses major obstacles to the identification of non-N⁶-methyladenosine mRNA modifications: their low abundance and the nonspecificity of many modifiers. The authors further discuss the enrichment of mRNA modifications in distinct cell compartments and physiological conditions.

In this Perspective, the authors propose that transcription at enhancers and transcription at their cognate genes are linked, forming the basis of enhancer–gene communication. This model represents a synthesis of recent key discoveries.

Here, the authors discuss dual-reporter systems and confounding variables that may lead to misinterpretation of results. They propose guidelines for robust design, physiological interpretation and accurate reporting when using dual reporters.

In this perspective, the authors showcase the importance and need for additional investigation of the ubiquitin-dependent regulation of neurodevelopment. They then propose interdisciplinary approaches that will allow improved spatiotemporal understanding of this relationship in the context of basic neuroscience and disease.

In this Perspective, the authors propose a framework to explain membrane protein biogenesis, wherein different parts of a nascent substrate are triaged between Oxa1 and SecY family members for insertion.

Hexasomes are non-canonical nucleosomes that package DNA with six instead of eight histones. Here, the author contextualizes two recent studies on the interplay of the chromatin remodeler INO80 with hexasomes with historical literature on the subject.

In this Perspective, the author describes the recent progress in understanding solute carrier (SLC) biology and discusses the roles of new families of atypical SLCs.

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.