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.

Two papers offer a first glimpse at complexes of the helicase-like domain of DNA polymerase θ (Polθ-HD) bound to DNA. Together, they provide structural insights into how the dimeric form of Polθ-HD grabs and aligns single-stranded DNA tails near the 3′ termini, a process that is accompanied by large conformational changes within Polθ-HD.

Jerelle Joseph is an assistant professor at the Department of Chemical and Biological Engineering and the Omenn–Darling Bioengineering Institute at Princeton University in New Jersey. We contacted Jerelle to learn about her research priorities, along with her thoughts about the biomolecular condensates field and how computational biology and molecular simulations can fuel discovery.

Multiplexed assays of variant effect can resolve clinical variants but are incompatible with secreted proteins. Here Popp et al. develop MultiSTEP, a generalizable surface-tethering method to assess variant effects in secreted proteins at scale.

Mei et al. profile H2A variant distribution in mouse oocytes, revealing broad H2A.Z domains at intergenic regions in which H2A.Z and MLL2-mediated H3K4me3 reinforce each other. H2A.Z is vital for oocyte development.

Xu et al. establish the importance of H2A.Z in mouse oocyte development. H2A.Z is incorporated into chromatin at promoters and putative enhancers, and its presence promotes histone acetylation in fully grown oocytes.

Here, Rangan et al. characterize S. cerevisiae intron structures with in vivo transcriptome-wide structure probing, showing that certain introns exhibit structural features that distinguish pre-mRNA from spliced mRNA and contain structures that regulate gene expression.

Here the authors uncover how a floppy tail in a protein acts as a remote switch, flipping activity on or off by tweaking internal motion, which reveals a powerful new way proteins regulate themselves without direct contact.

Guided by a structure of VGLUT2 with substrate, Li et al. identify the mechanisms for selective substrate recognition, a role for lipid modification in limiting axonal dispersion and for the cytoplasmic gate in allosteric regulation by lumenal H⁺.

We explain why we ask our authors to provide structural data prior to peer review.

Jerelle Joseph is an assistant professor at the Department of Chemical and Biological Engineering and the Omenn–Darling Bioengineering Institute at Princeton University in New Jersey. We contacted Jerelle to learn about her research priorities, along with her thoughts about the biomolecular condensates field and how computational biology and molecular simulations can fuel discovery.