BioEssays

Olecka, Maja; Morrison, Helen; Hoffmann, Steve

doi: 10.1002/bies.202400222pmid: 40091296

The traditional view of aging as a gradual, progressive process is increasingly being challenged. A growing body of evidence suggests the existence of abrupt transitions in the aging process, marked by sudden molecular shifts. Interestingly, the data indicates that such transitions occur not only in late life but also throughout the entire lifespan. Further research on the nature of such events could enhance our understanding of aging and pave the way for novel therapeutic strategies, including personalized medicine. We propose that these abrupt molecular shifts could serve as biomarkers, dividing the lifespan into distinct stages and providing the foundation for a much‐needed staging system for aging. Furthermore, we argue that the sudden changes may be the hallmarks of aging tipping points, that is, points in time where aging processes are quickly amplified after surpassing critical biological thresholds.

Hwang, Jiwon; Lauinger, Linda; Kaiser, Peter

doi: 10.1002/bies.202400249pmid: 40091294

Cullin‐RING ligases (CRLs) are central regulators of environmental and cellular stress responses, orchestrating diverse processes through the ubiquitination of substrate proteins. As modular complexes, CRLs employ substrate‐specific adaptors to target proteins for degradation and other ubiquitin‐mediated processes, enabling dynamic adaptation to environmental cues. Recent advances have highlighted the largest CRL subfamily SCF (Skp1‐cullin‐F‐box) in environmental sensing, a role historically underappreciated for SCF ubiquitin ligases. Notably, emerging evidence suggests that the F‐box domain, a 50‐amino acid motif traditionally recognized for mediating protein‐protein interactions, can act as a direct environmental sensor due to its ability to bind heavy metals. Despite these advances, the roles of many CRL components in environmental sensing remain poorly understood. This review provides an overview of CRLs in stress response regulation and emphasizes the emerging functions of F‐box proteins in environmental adaptation.

Izard, Tina

doi: 10.1002/bies.202400276pmid: 40012268

Talin, a key integrin activator, is essential for cellular adhesion, signal transduction, and mechanical stability. Its transition between autoinhibited and active conformations allows dynamic regulation of adhesion in response to environmental cues. Cholesterol‐rich membrane microdomains, such as lipid rafts, organize and stabilize signaling platforms, influencing talin and integrin conformational states. Cholesterol is a switch modulating talin activation, integrin binding, and adhesion. Environmental pollutants, including heavy metals and air toxins, disrupt cholesterol homeostasis, destabilize lipid rafts, and interfere with talin–integrin interactions. These disruptions impair adhesion, tissue repair, and signaling fidelity, contributing to atherosclerosis and cancer metastasis. Understanding talin's interaction with cholesterol‐rich domains offers critical insights into adhesion regulation and reveals the broader impact of environmental toxicants on cellular function. This framework emphasizes the importance of membrane composition, particularly cholesterol, in mediating the effects of environmental stressors and suggests potential therapeutic interventions.

Mantica, Federica; Irimia, Manuel

doi: 10.1002/bies.202400202pmid: 39995355

Animals comprise hundreds of cell types, each with specialized biological functions. However, many genes expressed in each cell type belong to widely conserved gene families with ancestrally ubiquitous expression. This raises a paradox: how have these genes evolved to shape cell type‐specific traits without compromising their ancestral function in all other cells? This can be achieved through gene duplication and the origin of regulated, alternatively spliced exons, which generate new related proteins in the form of paralogous genes and alternative isoforms, respectively. Here, we explore how such new related proteins can contribute to the evolution of specific cell types while preserving broader ancestral roles. Specifically, we separately classify possible expression and functional fates for new related proteins and discuss their interplays and evolutionary likelihood. Our primary hypothesis is that expression specialization, mostly coupled with functional specialization, is the predominant fate for both paralogous genes and alternative isoforms throughout animal evolution.

Lee, Yuh‐Ru Julie; Liu, Bo

doi: 10.1002/bies.202500004pmid: 40025940

Plant cytokinesis results in the formation of the cell plate by the phragmoplast which contains dynamic microtubules serving as the track for the delivery of cell wall builders included in Golgi vesicles. During the centrifugal process of cell plate assembly, new microtubules are assembled and bundled at the leading edge to prepare for vesicle transport while older microtubules are disassembled at the lagging edge upon the completion of vesicle delivery. The turnover of phragmoplast microtubules in this process is thought to be regulated by phosphorylation of the key microtubule bundling factor MAP65. A recent study revealed a surprising role of the α‐Aurora kinase, which is typically known for its role in governing the formation of the bipolar spindle apparatus, in phosphorylating the primary microtubule bundler MAP65‐3 in Arabidopsis. This phosphorylation positively contributes to the expansion of the phragmoplast. The phragmoplast midzone is also the hub for other cytokinesis‐important kinases. It is intriguing how these kinases are targeted and how they may crosstalk with each other to orchestrate the expansion of the phragmoplast.

doi: 10.1002/bies.70011pmid: N/A

Du, Yanfei; Wang, Chenhui; Zhang, Yu; Liu, Huiquan

doi: 10.1002/bies.202400220pmid: 39981820

Adenosine‐to‐inosine (A‐to‐I) RNA editing, capable of protein recoding, has evolved independently in animals and fungi. This study proposes adaptive hypotheses regarding its origins and phenotypic significance, suggesting that A‐to‐I editing enhances adaptability by alleviating genetic trade‐offs. In metazoans, its emergence may have been driven by a development‐defense trade‐off associated with transposable element activation during the evolution of multicellularity. Late Devonian cooling and End‐Permian warming are hypothesized to have driven the emergence of extensive A‐to‐I recoding in coleoid nervous systems and Sordariomycete sexual fruiting bodies, respectively. These adaptations may have influenced key evolutionary innovations, including the evolution of metazoan nervous systems, coleoid intelligence, and shell loss, and fungal sexual reproductive structures. Additionally, extensive A‐to‐I recoding is proposed to facilitate accelerated development and specific life‐history strategies in both animals and fungi. This paper provides new perspectives on the evolutionary forces shaping A‐to‐I RNA editing and its role in phenotypic diversity across taxa.

Crawford, Callie E. W.; Burslem, George M.

doi: 10.1002/bies.202500035pmid: 40091300

Wilmott, Patrick; Lisowski, Leszek

doi: 10.1002/bies.202400266pmid: 40045668

Intra‐strand base pairing is possible when double‐stranded DNA contains inverted repeats, but vanishingly improbable without so‐called negative superhelicity. This superhelicity itself is conditional upon whether the molecule can retain torsional stress—a question of “topology.” This principle has been uncontroversial to biophysicists since the 1980s but has proven challenging for outsiders to grasp and retain. For those in AAV research, this constitutes a decades‐long missed connection. AAV is one of a multitude of viruses bearing secondary‐structure‐forming elements on their termini. Its “inverted terminal repeats” (ITRs) can self‐anneal into relatively large hammerhead structures on both ends of the dynamically structured genome and are central to numerous host interactions that drive the viral lifecycle. A standalone article such as this is therefore warranted to promote an understanding of these ideas in the AAV research community and highlight their significance in the basic biology of the virus and its vector gene delivery system.