Two recent studies provide mechanistic insights into how LIN28A controls changes in cell fate identity, focusing on either a let-7-independent or let-7-dependent pathway of action involving LIN28A.

Snowflakes, seashells and Romanesco broccoli are striking examples of fractal geometries in nature. A recent study published in Nature defines a set of molecular mechanisms for fractal assembly by identifying a nanometer-scale, regular fractal assembled from a native protein found in blue-green algae that likely arose as an evolutionary accident.

AlphaFold 3 represents a breakthrough in predicting the 3D structures of complexes directly from their sequences, offering insights into biomolecular interactions. Extending predictions to molecular behavior and function requires a shift from viewing biomolecules as static 3D structures to dynamic conformational ensembles.

Poxviruses range from deadly smallpox to attenuated vaccinia virus used in vaccines and oncolytic vectors. Despite their broad, if antithetical, effects on humankind, the mechanistic details of poxvirus assembly are not known. Here we discuss advances in revealing the structure of the palisade layer which underlies the viral core morphology.

Cryo-electron microscopy reveals the mechanism of human translation initiation from codon scanning to subunit joining. The structures show the roles of the Kozak sequence, GTP hydrolysis by eukaryotic initiation factor 2 (eIF2) and eIF5B in 48S remodeling, as well as that of eIF3 in the control of 60S docking.

Here, the authors show that bromodomain-containing protein 4 is recruited to the MYC enhancer by Mediator and activates transcription through elongation factors independently of bromodomains. This mechanism contributes to bromodomain and extraterminal domain inhibitor resistance in estrogen receptor-positive breast cancer.

Exocytosis of secretory vesicles is required for cellular growth, cellular division and cell–cell communication. Lee et al. reveal that the exocyst tethering complex has stimulatory roles in exocytic soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly and SNARE-mediated vesicle fusion.

Using cryo-electron tomography of human T cell leukemia virus type 1 virus-like particles, the authors reveal that the immature Gag lattice is stabilized by the capsid N-terminal domain in contrast to other retroviruses that use the C-terminal domain.

Germline small RNAs in plants and mammals are marked by pseudouridine. In plants, Exportin-t is required for pseudouridylation, transport and localization of small RNAs in pollen, as well as for epigenetic inheritance in the form the triploid block.

Anti-NMDA receptor encephalitis is the most common autoimmune encephalitis. Michalski et al. reveal epitope diversity, conformational changes and functional impacts of the autoantibodies using cryo-EM and electrophysiology.

The idea of a scientific discovery is often linked to the eureka moment of a lone scientist, which then transforms our thinking. However, scientific discoveries are never made by individuals in isolation. They build on the work of countless researchers, and often require interdisciplinary and collaborative teams of researchers.

Curiosity-driven and fundamental discovery science must be justified in its importance to human health and translational potential for practical applications and cures. However, many groundbreaking discoveries occur through the freedom to ask fundamental questions — the how and why — without knowing where they lead. Presented here is an example of a clinical target that emerged from a seemingly simple question in chromosome biology.

Macromolecules are involved in myriads of interactions that regulate their cellular function. While years of structural biology progress was built by reducing this complexity, a molecular understanding of biological processes requires the characterization of ever larger and more dynamic molecular assemblies. Cryo-electron microscopy is rising to this challenge.

This issue of Nature Structural & Molecular Biology presents studies investigating RNA processing, including mechanisms of splicing, biogenesis of the splicing machinery, decoding of mRNA by the ribosome, and deadenylation of mRNA for degradation. We are also delighted to be publishing News & Views and Comment pieces that reflect on these exciting advances in the field.

Since Nature Structural and Molecular Biology was started 30 years ago, our understanding of transcription and mRNA processing has been revolutionized through structural and mechanistic studies. Here, we present our personal views of the advances in understanding the production of mature eukaryotic mRNAs over the past decade.