Closing 2025, and a look ahead

We review 2025 and discuss some of the foremost initiatives developed at the journal. We also look back at discoveries we have been proud to publish.

On our final cover of the year, we highlight a study leveraging region-capture Micro-C to show that, surprisingly, chromatin microcompartments not only form during mitosis to G1 but are also dynamically regulated. We are inspired by the use of cutting-edge, high-resolution genomics techniques to tackle open questions in the biology of chromatin, epigenetics and the cell cycle, and look forward to many more developments in this field. This issue includes more must-read articles for structural, molecular and cell biologists.

The AlphaFold Database (AFDB), which harbors all protein structures predicted using the AlphaFold structure prediction tool, is becoming a standard tool for researchers. The AFDB aims to house all known and annotated proteins. However, this set is constantly updated, corrected and expanded upon in the UniProt protein sequence Knowledgebase. As such, the AFDB (a static database) ages with time, with predicted structures not always being based on the most updated sequences. The aging of bioinformatics databases is discussed in a Comment in this issue. To address this, Babu and colleagues generated AlphaSync, which syncs the AFDB with the latest UniProt version on an external server. The EMBL-EBI and Google DeepMind have announced that they are renewing their partnership and releasing an update to the AFDB. As per this press release, the AFDB has been synchronized with the UniProt March 2025 release. This is a welcome announcement, highlighting the importance of, and work that goes into, keeping the different databases up to date. We hope the discussion and new tools published in this issue will help researchers obtain the most accurate data and predictions possible.

As the year closes, we look back at our favorite updates to the journal. We made progress in enhancing the rigor and transparency of data reporting standards. Our journal now has a workflow for peer-reviewing cryo-EM data¹. We also encourage our authors to include a minimal reporting table for light microscopy experiments² as part of a pilot across the portfolio. These efforts ensure more thorough, standardized and direct peer review of these data types. We are also happy to be working toward increased engagement of early career researchers as reviewers, by inviting all referees to co-review with more junior colleagues³.

Our team dedicated efforts to diversify the news and opinion content we publish and to increase the diversity of voices we amplify⁴. Our first world view series explores the challenges and rewards of returning to one’s home country to continue academic research. Our Q&A and viewpoint pieces allow us to explore an array of topics and highlight the researchers at the forefront of these fields.

We are delighted to have continued to publish authoritative, forward-looking and insightful reviews and perspectives. Atari, Jiang and Greenberg⁵ provided a comprehensive overview of the mechanisms of break-induced replication, a type of DNA repair relevant for genome stability at telomeres and in cancer. Altendorfer, Mundlos and Mayer⁶ focused on the emerging evidence that links enhancer transcription to enhancer–gene and enhancer–promoter communication. In a Review, Abshire and Maquat recapitulated the functions of the splicing exon junction complex in regulating gene expression.

We are proud to have published a special issue dedicated to ubiquitin and protein degradation⁷ — our second special issue of this kind. We look forward to more state-of-the-art studies providing conceptual advances in less understood areas, such as atypical ubiquitin chains and non-protein ubiquitylation, while retaining a keen interest in work developing glues or PROTACs (proteolysis-targeting chimeras) that target key factors in autophagy, cancer and neurodegeneration. In addition, our publications have included more mechanistic work that delineate processes of wide interest and importance. For example, the work of Miao et al.⁸ examines the cell type-specific mechanisms by which loss of an organelle contact site protein, VPS13D, leads to cell death.

We remain interested in the molecular details central to the flow of genetic information from gene to protein and are always excited when biological players are discovered to have unforeseen functions, such as the paper by Bartuli et al.⁹ that shows a function of tRNA as a chaperone in the assembly of a multi-subunit viral polymerase. Moreover, we are continuing to publish advances in research into the cytoskeleton across biological scales. Among those, Chai, Yang et al.¹⁰ solved a multitude of cryo-EM structures of dynein 1, revealing a variety of conformational states that provide deep mechanistic insights into the movement cycle of this motor protein. Our content has also included methodological advances, such as pioneering, systems-level proteomics methods that allow protein glycosylation profiling with DQGlyco¹¹ or mapping of protein–ligand interactions with HT-PELSA¹².

We have been proud to call for papers in research domains that have defined, and will continue to define, the journal: artificial intelligence methodology in structural biology, DNA repair and human disease and methods development in cryo-ET and in situ structural determination. With our sister journals in those collections, we are excited to consider work that address major open questions and ongoing challenges for those fields.

We thank our readers, authors and reviewers for continuing to support the journal, and we look forward to 2026 and more opportunities to support our community and shed light on exciting discoveries across our scope.