ABSTRACT Telomere biology is often framed as a uniquely eukaryotic problem, yet the challenges of maintaining DNA ends are shared by all organisms harboring linear DNA, including viral entities. Telomeres enable complete replication of chromosome ends while shielding the termini from DNA repair factors and innate immune surveillance systems that would otherwise recognize them as damaged or foreign DNA. A particular threat is posed by Mre11‐Rad50, a nuclease complex conserved from bacteria to humans that specializes in the detection and processing of DNA ends. The solutions to these DNA end‐related challenges that have emerged across the tree of life converge on a small number of recurring strategies. Here, we review how diverse biological systems, from bacteriophages to mammals, have solved the DNA end‐related challenges, with a particular focus on recent advances in our understanding of end protection.
ABSTRACT Recent studies indicate that PIWI (P‐element‐induced WImpy testis) like proteins and their cognate PIWI‐interacting RNAs (piRNAs), initially identified in germline cells for protecting genomic stability by transposon silencing, also exert multiple regulatory functions in somatic and immune systems. Additionally, PIWIL/piRNA pathways are linked to innate antiviral defense and immune signaling pathway regulation. This review systematically compiles the reports on the immunological functions of noncoding RNAs (ncRNAs) and delineates the potential molecular processes and functional characteristics of PIWIL/piRNA pathways. We propose that PIWIL/piRNAs function as a molecular link between adaptive and reproductive immunity and maintain barrier integrity in immune‐privileged settings. Predictive bioinformatic analysis further revealed specific piRNAs that could interact with long noncoding RNAs (lncRNAs) and miRNAs to regulate immune response components within the TLR and JAK/STAT pathways, highlighting their potential role in antiviral and immunomodulatory signaling networks. We conclude by discussing the emerging opportunities to integrate ncRNA‐mediated regulatory mechanisms into personalized medicine and targeted therapies while addressing the key hurdles in clinical application.
ABSTRACT The prevailing view of biological evolution is not unlike bricolage/pastiche/tinkering—in sharp contrast with rational engineering. Yet, different paths often lead to solutions that coincide or converge whether they emerge from naturally‐occurring evolution or rationally designed. Such a conjunction—often presented as an anecdote—reveals the ability of biological systems to explore solution spaces and gravitate toward information‐rich attractors, which can be found through different routes. This scenario evokes one of embodied computing, a non‐conventional type of data processing in which the solution to a problem is not delivered through numerical calculations but through its implementation in a material object. Once left to undergo a physical process the object manages a large number of parameters for reaching a multi objective optimum through thermodynamically‐driven processes. The course of information is thus a physical flow and the outcome is a physical currency. The consequences of this notion for bioengineering are remarkable.
ABSTRACT Where a transcript goes among a cell's membraneless compartments—stress granules, P‐bodies, paraspeckles, nuclear speckles—is an addressable, rewritable property that this article proposes chemical modifications of RNA help write. The code's output depends on the transcript's role: for client messenger RNAs, an apparent partition coefficient (K part ), its enrichment in a condensate; for the rare long noncoding RNAs acting as architectural scaffolds, the saturation concentration that decides whether the compartment forms at all. This client/scaffold asymmetry is the framework's central proposal, its scaffold arm as yet untested. Only m6A has cellular partitioning evidence; A‐to‐I editing sets nuclear address by a related route, and the remaining marks are candidates or structure‐based predictions. The value is a variable and a falsifiable test: perturb a mark at fixed sequence and state, and ask whether the address moves. It reframes scattered epitranscriptomic and condensate biology as one control problem.
ABSTRACT The concept of ‘metabolic structure’, which considers metabolism as a stable, genetically encoded architecture with enzymes occupying fixed control positions, is indispensable but incomplete, and it obscures metabolism's true nature. I propose redefining metabolism as a dynamic field of emergent biochemical fluxes, governed by six fundamental parameters: time, water, entropy, quantum effects, space, and electrostatic potential, shaping the thermodynamic trajectories of living matter. Metabolic control analysis already supports this view: flux control coefficients are state‐ and time‐dependent coordinates within a thermodynamic field, not intrinsic enzyme properties. This perspective manifests across scales: electrostatics govern fructose 1,6‐bisphosphate cleavage in aldolase; hepatic zonation shows spatial reorganization through a single parameter; glucose deprivation quantitatively redirects intestinal cancer cell metabolism from glycolytic to oxidative flux, driving differentiation into an enterocyte‐like state; post‐meal walking redirects glucose flux from storage to oxidation without pharmacological intervention; inherited metabolic diseases can sometimes be managed without correcting the causal mutation. These examples converge into a new framework: metabolism possesses not only a sophisticated architecture but also states that shape its fluxes. And states, unlike static structures, can be reconfigured.
