Review Articles

Amplification of oncogene expression through extrachromosomal DNA is a common feature of many cancers and is associated with poor outcomes. Hung et al. review how regulation of extrachromosomal DNA gene expression is linked to alterations in chromatin structure and changes in contacts with DNA regulatory elements.

The organization of multiple steps of the RNA life cycle in phase-separated condensates presents a framework for understanding how sequestration of RNA-binding proteins and RNAs modulates gene expression.

Sfeir and colleagues consider recent insights into the pathways that process and repair damaged mitochondrial genomes, nuclear–mitochondrial cross-talk during mtDNA stress, and links between mtDNA dysfunction and innate immunity.

Small molecules that hijack the cellular protein ubiquitination machinery to selectively degrade proteins of interest have emerged as therapeutic modalities and powerful research tools. This Review summarizes recent developments in this field, with a focus on the use of degraders as research tools.

Lauberth and Sartorelli consider and discuss recent insights into the biogenesis and function of enhancer RNAs and the key roles they play in the regulation of gene expression.

Technological advances have led to new insights into genome-wide arrangements of nucleosomes along the DNA and the folding of the chromosome fiber in nuclear space, revealing unexpected diversity.

Husmann and Gozani review the biochemical and biological activities of histone lysine methyltransferases and their connections to human diseases, focusing on cancer.

Zaware and Zhou review the current understanding of bromodomain biology and discuss the latest development of small-molecule inhibitors that target these protein domains as emerging therapies for cancer and inflammatory disorders.

This review proposes an up-to-date, consensus thermodynamic model for the conformational changes associated with transport by the eukaryotic type I exporters from the ABC family and discusses structural insights into ABC transporter pharmacology.

In this Review, Bob Roeder offers a personal, historical perspective of the landmark studies that elucidated the mechanism and regulation of eukaryotic transcription over five decades, from the initial discovery of three nuclear RNA polymerases to the structural, genomic and imaging approaches that continue to expand our understanding of the function of complex regulatory networks.

Bryan Roth reviews how insights into the structures of G protein–coupled receptors that are targets of neuropsychiatric drugs contribute to understanding of their functions as well as to the discovery of new chemical tools and drugs.

Monoamine transporters (MATs) regulate neurotransmission via the reuptake of dopamine, serotonin and norepinephrine from the extra-neuronal space. This Review discusses recent advances in elucidating the structural dynamics and allosteric regulation of MATs.

Numerous proteins in dendrites and axons are synthesized locally. In this Review, the authors summarize current evidence for local mRNA translation in neurons and discuss the neuronal functions shown to be served by this process.

In this Review, Wiedenheft and colleagues retrace events that led from early endeavours to understand the role of Cas9 in CRISPR-mediated adaptive immunity to current efforts aimed at developing this enzyme for programmable genetic editing.

Shah and Kuriyan highlight how the analysis of sequence variation synergizes with protein structure information, to provide new insights into specificity and allosteric regulation of signaling proteins.

Zhou, Gaullier and Luger review insights derived from cutting-edge biophysical and structural approaches applied to the study of nucleosome dynamics and nucleosome-binding factors, with a focus on the experimental advances driving the research.

This Review discusses mechanistic insights into 5´–3´ RNA decay, such as translation–decay coupling, coordination between complexes that process 5´ & 3´ RNA termini, conformational control of enzymatic activity, phase separation, & RNA modifications.

Cross-linking mass spectrometry has developed into a robust and flexible tool that provides medium-resolution structural information. This review highlights notable successes of this technique and discusses common pipelines.

In this Review, Haoxing Xu and colleagues summarize current knowledge of TRP channels and their roles in the response to environmental and cellular signals, focusing in particular on the least known class, the organellar TRPs.

Cramer and colleagues review and discuss how the structural elucidation of transcription factors and functional complexes of human mitochondrial RNA polymerase have informed emerging understanding of the mechanism of mitochondrial gene transcription.