Table of Contents Alert: The FEBS Journal, Vol. 293, No. 12, June 2026
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The FEBS Journal Volume 293, Issue 12 Pages: 3419-3705 June 2026
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Issue Information
Free AccessIssue Information
Pages: 3419-3422 | First Published: 18 June 2026
Cover Illustration
Structural characterization of DNAJC7 JD and the ALS-associated E425K mutant. Image courtesy of Rina Rosenzweig and colleagues, authors of the Original article included in this issue, pages 3485–3501.
State-of-the-Art Review
Open AccessPost‐transcriptional regulatory networks: The dynamic interplay of RNA‐binding proteins
Pages: 3423-3441 | First Published: 01 April 2026
Post-transcriptional gene expression regulation is controlled by RNA-binding proteins (RBPs), which influence many processes including splicing, localization, translation, and decay. Rather than acting alone, RBPs bind RNAs combinatorially, forming complex, context-dependent regulatory networks. Recent advances, including multiplexed RBP–RNA-binding assays, interaction proteomics, RNA pulldowns, imaging, and high-throughput screens, are enabling systems-level mapping of these networks, advancing understanding of coordinated RNA regulation and its disruption in disease.
Structural Snapshot
Structural heterogeneity of apolipoprotein B‐100
Pages: 3442-3451 | First Published: 17 February 2026
Cardiovascular disease is the leading cause of human mortality. A major factor in the development of atherosclerosis is elevated plasma levels of low-density lipoproteins (LDL), which contain a single copy of apolipoprotein B-100 (apoB-100). Drug strategies for disease prevention are largely centered on the interaction of low-density lipoprotein receptor (LDLR) with LDL. This review discusses recent structural information on this interaction as well as the structural heterogeneity observed in apoB-100.
Structural features of a new class of terpenoid cyclases
Pages: 3452-3460 | First Published: 24 February 2026
Here, we summarise the structural features of BcABA3 and its homologues. ABA3 proteins adopt an all-α-helix fold and utilise a distinct substrate-binding mode to catalyse FPP cyclisation. These enzymes contain a Mg2+ ion-coordinating Glu, a PPi-interacting RY pair, a Zn2+ ion-binding motif, and a KLW motif-harbouring lid that seals the catalytic centre, providing a valuable foundation for further investigations into this new class of terpenoid cyclases.
Commentary
Open AccessIntermediate filaments link glutamate–aspartate transporter deficiency to cochlear synaptopathy
Pages: 3461-3465 | First Published: 01 April 2026
In a healthy ear, GLAST transporters in supporting cells clear excess glutamate to protect auditory connections. When GLAST is missing, glutamate accumulates and leads to the destruction of structural scaffolding within the postsynaptic nerve endings. This internal collapse causes a loss of synapses that are essential for hearing, ultimately resulting in a condition known as ‘hidden hearing loss’ and accelerating age-related hearing decline.
Comment on: https://doi.org/10.1111/febs.70368.
Open AccessHolding but not folding: How a single charge flip uncouples the DNAJC7‐Hsp70 relay in amyotrophic lateral sclerosis
Pages: 3466-3469 | First Published: 23 February 2026
In this issue, Elmaleh et al. demonstrate that the E425K mutation in DNAJC7, associated with amyotrophic lateral sclerosis, selectively abolishes one of a co-chaperone's dual functions. High-resolution NMR confirmed that the mutation leaves the protein's structure intact while paralyzing its communication with the Hsp70 machinery. The mechanistic results complement in vivo studies of ALS disease pathology and present a new strategy to rescue non-functioning Hsp70 chaperone systems.
Original Article
Editor's Choice
Impaired postsynaptic function and disruption of intermediate filaments in GLAST‐knockout‐induced hidden hearing loss
Pages: 3470-3484 | First Published: 26 December 2025
Hidden hearing loss (HHL) is an inner ear disorder characterized by synaptopathy despite normal hearing thresholds. This study sought to clarify the underlying molecular mechanisms of HHL in a mouse model. Glutamate-aspartate transporter (GLAST) serves as the major glutamate transporter in the inner ear, preventing excitotoxicity. GLAST-deficient mice exhibit characteristic features of HHL. We observed decreased surface expression of postsynaptic proteins and disruption of the cytoskeleton, particularly the intermediate filaments, in GLAST knockout mice at 2 months. Furthermore, these GLAST-deficient mice developed accelerated age-related hearing loss at 5 months, primarily due to the degeneration of outer hair cells. Our findings indicate that loss of GLAST induces synaptopathy, disrupts intermediate filament organization, and accelerates age-related hearing loss, providing insights into HHL development and its progression to overt hearing loss.
Open AccessThe ALS‐associated E425K mutation uncouples DNAJC7 from the Hsp70 chaperone cycle
Pages: 3485-3501 | First Published: 14 January 2026
DNAJC7 is a J-domain protein that plays a key role in protein quality control by regulating Hsp70 activity and preventing protein aggregation. We find that the ALS-associated E425K mutation in DNAJC7 disrupts productive interaction and activation of Hsp70, thereby blocking the transfer and refolding of client proteins such as TDP-43. This results in the accumulation of misfolded TDP-43, providing a mechanistic basis for how the E425K mutation impairs proteostasis in ALS.
Open AccessRegulation of PHOX2B gene expression by the long non‐coding natural antisense RNA PHOX2B‐AS1
Pages: 3502-3527 | First Published: 24 January 2026
PHOX2B is a transcription factor essential for autonomic nervous system development. We identify and characterize PHOX2B-AS1, a human long non-coding antisense transcript at the PHOX2B locus, along with its murine counterpart. Our findings reveal bidirectional transcription and reciprocal regulation: PHOX2B activates PHOX2B-AS1, whereas PHOX2B-AS1 inhibition reduces PHOX2B protein levels. This highlights a critical regulatory interplay between sense and antisense transcription at the PHOX2B locus.
Open AccessSelective targeting of cortactin tandem repeat acetylation by human lysine deacetylases
Pages: 3528-3544 | First Published: 04 February 2026
Cortactin function is regulated by acetylation at several lysine residues within its tandem repeat region. Using genetic code expansion to generate cortactin variants containing precisely defined acetylation marks, we show that HDAC6 is the primary enzyme removing these modifications, with SIRT1 and SIRT2 also acting at selected sites but with lower efficiency.
Biochemical characterization and mutational analysis of the tetrameric DABA transaminase EctB from the Arctic bacterium Marinobacter sp. CK1
Pages: 3545-3564 | First Published: 06 February 2026
The EctB enzyme from the Arctic bacterium Marinobacter sp. CK1 catalyzes a key step in ectoine biosynthesis, converting l-aspartate-β-semialdehyde to l-2,4-diaminobutyric acid. Structural and mutational analyses highlighted the importance of tetramerization and critical residues for activity and stability. While some mutations improved thermal stability, others disrupted oligomerization and abolished activity. These findings support optimizing EctB in industrial ectoine production and its application as a transaminase in green chemistry.
Open AccessEnergetic stress in combination with impaired fatty acid oxidation induces sequestration of CoA and adaptation of CoA metabolism
Pages: 3565-3587 | First Published: 07 February 2026
Computational modelling and in vitro liver cell experiments indicate that medium-chain acyl-CoA dehydrogenase (MCAD) deficiency causes an accumulation of (especially medium-chain) acyl-CoAs at the cost of free CoA (CoASH). A substantial decrease in CoASH impairs flux through many pathways essential for energy homeostasis. MCAD-knockout mice, in response, upregulate CoASH production and acyl-CoA-cleaving pathways.
Open AccessUncovering a previously unknown function of polyphosphate in polyadenylated RNA‐induced amyloidogenesis of Hfq
Pages: 3588-3600 | First Published: 09 February 2026
Polyphosphate interaction with Hfq and RNA drives phase separation and amyloid self-assembly, uncovering a previously unrecognized role for polyP in bacterial stress responses. Our findings reveal new insights into the molecular mechanisms of RNA-mediated phase separation, highlighting the role of polyP as a key modulator of this process.
Open AccessComparative evaluation of noncanonical amino acids as site‐specific NMR probes for the complex of E. coli SSB with single‐stranded DNA without isotope labelling
Pages: 3601-3620 | First Published: 10 February 2026
Genetic encoding of noncanonical amino acids (ncAA) enables their site-specific installation in proteins. This work compares the nuclear magnetic resonance (NMR) performance of different ncAAs in a large protein−DNA complex (~ 100 kDa) without isotope labelling. The ncAAs deliver readily detectable NMR signals in the complex between E. coli single-stranded DNA-binding protein (SSB) and single-stranded DNA (ssDNA), revealing very similar interactions of each SSB monomer with the ssDNA.
Identification of Wnt‐regulated genes that are repressed by, or independent of, β‐catenin
Pages: 3621-3639 | First Published: 28 January 2026
Wnts are well-known to activate and repress transcription via stabilized β-catenin: how much transcription is Wnt-regulated but β-catenin independent? Testing this in an orthotopic pancreatic cancer model, we find that only 10% of Wnt-regulated genes are β-catenin independent. Additionally, we provide strong evidence for a Wnt negative response element (NRE) that contributes to widespread Wnt-mediated gene repression.
Deciphering the structural insights and concentration‐dependent dimerisation of endo‐β‐1,4‐xylanase (AcXyn30B_12) from Acetivibrio clariflavus using SAXS and computational methods
Pages: 3640-3662 | First Published: 13 February 2026
This infographic presents a comprehensive workflow for characterising endo-xylanase enzyme, AcXyn30B_12. It integrates molecular docking, dynamics and SAXS/DLS to reveal a strong binding affinity and structural compactness. Protein expression was confirmed via SDS/PAGE, while CD spectroscopy indicated balanced α-helix and β-sheet content. The 3D model highlights catalytic and CBM domains, supporting a retaining mechanism. Together, these techniques validate the protein's structure–function relationship and ligand specificity.
Open AccessAnti‐cancer drugs targeting the NADH‐binding site of VDAC rewire channel electrophysiology and partially suppress cation selectivity
Pages: 3663-3682 | First Published: 09 February 2026
VA molecules alter VDAC1 gating by increasing anion flow and reducing cation permeability. In cancer cells, which rely on ER-mitochondria Ca2+ transfer and overexpress VDAC1, this imbalance triggers bioenergetic stress, ROS buildup, and mitochondrial collapse, leading to cell death. In normal cells – where VDAC1 is not overexpressed – changes in channel ion conductance do not impair mitochondrial function. Rather, they slow proliferation and halt cell cycle progression, preventing energetic failure.
Open AccessThe competitive interplay of 12‐oxophytodienoic acid (OPDA), protein thiols, and glutathione
Pages: 3683-3705 | First Published: 05 February 2026
12-Oxophytodienoic acid (OPDA) is a phytohormone involved in plant growth and stress defense. Due to its cyclopentenone moiety, OPDA can form Michael adducts with thiol-containing compounds such as glutathione and cysteine residues of proteins, resulting in alterations of the cellular redox regulatory network. Our findings reveal transferability of OPDA between OPDA adducts, indicating a novel regulatory mechanism of OPDA signaling which allows for fine-tuning of OPDA signaling.
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