The ROP subfamily of Rho GTPases act as a key signaling switch in response to the phytohormone auxin, impacting auxin response and transport in plant growth and development. It remains unknown whether auxin biosynthesis is regulated by ROP. Using Arabidopsis root hairs as a system to study cell growth, we found that ROP2/4/6 GTPases act redundantly in root hair growth via control of YUC-dependent auxin biosynthesis. The rop2/4/6 mutant reduced root hair growth, auxin accumulation and transcription of all 11 YUC auxin biosynthesis genes. External auxin and overexpression, root hair specific or shoot-specific expression of YUC2/8 fully restored rop2/4/6 root hair growth. A phosphomimetic (S5D) mutation in the C-terminal domain (CTD) of RNA polymerase II RPB1 increased YUC2/8 expression and hair growth in rop2/4/6, linking the Pol II CTD phosphorylation code to ROP-mediated YUC transcription. Our results reveal auxin biosynthesis as another important regulatory layer for ROP function during cell growth.
Seasonal influenza vaccines require annual reformulation due to antigenic drift and provide suboptimal protection. Here, we evaluate self-amplifying mRNA (samRNA) vaccines encoding chimeric (cHA) and mosaic (mHA) hemagglutinins representing influenza A virus HA phylogenetic groups 1 and 2. Following prime-boost immunization, group 1 cHA vaccines (cH8/1-cH5/1) elicit broad cross-reactive antibodies and confer complete protection against diverse H1N1 strains covering decades of antigenic drift. Group 2 vaccines (cH4/3-cH15/3 and mH10/3-mH14/3) provide comparable breadth against multiple H3N2 strains and heterosubtypic H7N9 challenge, with cHA samRNA showing superior cross-group protection. Protection is associated with Fc-mediated effector functions and CD4+ T cell responses, with minimal hemagglutination inhibition and neutralizing titers. Passive serum transfer confirms antibody-mediated protection independent of cellular immunity. Protective immunity is maintained at doses as low as 0.4 μg, demonstrating the dose-sparing advantage of the samRNA platform. These results support samRNA-delivered cHA and mHA antigens as promising candidates for broadly protective influenza vaccines.
The “closed-loop” mRNP, in which the 5′ cap and 3′ poly(A) tail are bridged by eIF4E-eIF4G-PABP interactions, has been proposed to drive efficient translation. Direct rigorous tests of this model in mammalian cells have remained elusive. Using auxin-inducible degrons to acutely deplete eIF4G1, we find that global translation is only partially reduced and recovers without restoration of eIF4G1 levels. We identify eIF4G3 as an underappreciated contributor to basal translation that buffers translational output upon eIF4G1 loss. eIF4G1 mutants reveal that PABP binding by eIF4G1 is dispensable for bulk protein synthesis. Further, PABP depletion has no immediate effect on protein synthesis but instead destabilizes poly(A) mRNA. In contrast, the N-terminal enteroviral cleavage product (2A-cpN) is a potent, dominant translational repressor that requires both PABP- and eIF4E-binding domains for inhibition. These findings suggest that the eIF4G-PABP closed-loop architecture is not required for productive initiation but may be actively co-opted for translational silencing.
Summary: Successful behavior depends on evaluating both what is present in the environment and how reliable that information is. Yet how neural populations represent reliability, and whether this representation is shared across cortical areas, remains unknown. Using two-photon calcium imaging of over 150,000 neurons in mouse visual cortices during presentations of coherent motion stimuli, we find that sensory reliability is encoded through coordinated changes in response amplitude, selectivity, and signal-to-noise ratio. These coherence-dependent response patterns are not fully accounted for by stimulus-based normalization models; rather, they track the distribution of motion energy across directions, while remaining relatively invariant to total motion energy. This multi-feature code is expressed at the single-neuron and population levels and is consistent across visual areas, suggesting a shared encoding scheme rather than area-specific computations. Together, these findings support a common population code for stimulus reliability across visual cortices.
Reactive oxygen species are typically elevated at inflammatory sites due to influx of large numbers of neutrophils and other myeloid cells that produce oxygen free radicals as microbicidal agents. However, although oxidative stress is frequently implicated as an initiator or amplifier of inflammation, particularly in the context of cancer, the key mediators of reactive oxygen-driven inflammation require clarification. Here we show that the redox-responsive transcription factor, Nrf2, can act as an enhancer of TNF- and IL-1-initiated inflammation. Silencing or deletion of the Nrf2 antagonist, Keap1, led to robustly enhanced TNF- or IL-1-driven inflammatory cytokine production. Conversely, suppression of Nrf2 activation blunted inflammation in the same contexts. Mechanistically, Nrf2 enhanced inflammation through cooperative interactions with p65 RelA at NFκB-regulated promoters. These observations reveal a direct link between the Keap1/Nrf2 reactive oxygen-sensing pathway and TNF- or IL-1-initiated inflammation and suggest that Nrf2 can act as a rheostat for NFκB-dependent inflammatory outputs.
