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.

Kuhm et al. reveal how human guanylate-binding protein 1 (GBP1) dimers self-associate to coat bacterial pathogens and uncover a guanosine triphosphate hydrolase-dependent membrane-remodeling activity of GBP1 that is crucial for intracellular immunity

On the basis of the assembly mechanism and structures of the human subcortical maternal complex, the authors provide a strategy for the diagnosis of reproductive disorders and the discovery of new infertility-associated SCMC variants.

The authors present structures of endosomal sorting complexes required for transport III family member vesicle-inducing protein in plastids 1, ranging from helical assemblies and stacked rings to flat carpets, providing insights into transitions dependent on membrane tubulation and curvature needed for forming different architectures involved in membrane remodeling.

Live-cell single-molecule imaging of pioneer transcription factors revealed a ‘confined target search’ mechanism where they alternate between fast free diffusion in the nucleus and slower confined diffusion within compacted chromatin domains, leading to efficient pioneering on closed targets.

This study presents the cryo-electron microscopy structure of Fanzor2, showcasing its unique structural elements and nucleic acid interaction sites. A comparison to TnpB-related RNA-guided endonucleases highlights divergent evolutionary paths.

Here the authors experimentally describe the secondary structure of the NORAD long noncoding RNA in human cells. NORAD’s modular structure and specific structural elements allow it to efficiently antagonize the Pumilio RNA-binding proteins.

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.