hNUDT16: a universal decapping enzyme for small nucleolar RNA and cytoplasmic mRNA

Human NUDT16 (hNUDT16) is a decapping enzyme initially identified as the human homolog to the Xenopus laevis X29. As a metalloenzyme, hNUDT16 relies on divalent cations for its cap-hydrolysis activity to remove m⁷GDP and m²²⁷GDP from RNAs. Metal also determines substrate specificity of the enzyme. So far, only U8 small nucleolar RNA (snoRNA) has been identified as the substrate of hNUDT16 in the presence of Mg²⁺. Here we demonstrate that besides U8, hNUDT16 can also actively cleave the m⁷GDP cap from mRNAs in the presence of Mg²⁺ or Mn²⁺. We further show that hNUDT16 does not preferentially recognize U8 or mRNA substrates by our cross-inhibition and quantitative decapping assays. In addition, our mutagenesis analysis identifies several key residues involved in hydrolysis and confirms the key role of the REXXEE motif in catalysis. Finally an investigation into the subcellular localization of hNUDT16 revealed its abundance in both cytoplasm and nucleus. These findings extend the substrate spectrum of hNUDT16 beyond snoRNAs to also include mRNA, demonstrating the pleiotropic decapping activity of hNUDT16.     

The emergence of pandemic influenza viruses

Pandemic influenza has posed an increasing threat to public health worldwide in the last decade. In the 20th century, three human pandemic influenza outbreaks occurred in 1918, 1957 and 1968, causing significant mortality. A number of hypotheses have been proposed for the emergence and development of pandemic viruses, including direct introduction into humans from an avian origin and reassortment between avian and previously circulating human viruses, either directly in humans or via an intermediate mammalian host. However, the evolutionary history of the pandemic viruses has been controversial, largely due to the lack of background genetic information and rigorous phylogenetic analyses. The pandemic that emerged in early April 2009 in North America provides a unique opportunity to investigate its emergence and development both in human and animal aspects. Recent genetic analyses of data accumulated through long-term influenza surveillance provided insights into the emergence of this novel pandemic virus. In this review, we summarise the recent literature that describes the evolutionary pathway of the pandemic viruses. We also discuss the implications of these findings on the early detection and control of future pandemics.     

CGRP is essential for protection against alveolar epithelial cell necroptosis by activating the AMPK/L-OPA1 signaling pathway during acute lung injury

Alveolar epithelial cell (AEC) necroptosis is critical to disrupt the alveolar barrier and provoke acute lung injury (ALI). Here, we define calcitonin gene-related peptide (CGRP), the most abundant endogenous neuropeptide in the lung, as a novel modulator of AEC necroptosis in lipopolysaccharide (LPS)-induced ALI. Upon LPS-induced ALI, overexpression of Cgrp significantly mitigates the inflammatory response, alleviates lung tissue damage, and decreases AEC necroptosis. Similarly, CGRP alleviated AEC necroptosis under the LPS challenge in vitro. Previously, we identified that long optic atrophy 1 (L-OPA1) deficiency mediates mitochondrial fragmentation, leading to AEC necroptosis. In this study, we discovered that CGRP positively regulated mitochondrial fusion through stabilizing L-OPA1. Mechanistically, we elucidate that CGRP activates AMP-activated protein kinase (AMPK). Furthermore, the blockade of AMPK compromised the protective effect of CGRP against AEC necroptosis following the LPS challenge. Our study suggests that CRGP-mediated activation of the AMPK/L-OPA1 axis may have potent therapeutic benefits for patients with ALI or other diseases with necroptosis.     

Nitric oxide and hydrogen peroxide are important signals mediating the allelopathic response of Arabidopsis to p‐hydroxybenzoic acid

Both nitric oxide (NO) and hydrogen peroxide (H₂O₂) are important signals that mediate plant response to environmental stimulation. Their role in plants' allelopathic interactions has also been reported, but the underlying mechanism remains little understood. p‐Hydroxybenzoic acid (pHBA) has been proposed to be an allelopathic chemical. Here, we found that pHBA at 0.4 mM efficiently suppressed Arabidopsis growth. Meanwhile, pHBA rapidly induced the accumulation of NO and H₂O₂, where such effect could be reversed by NO or H₂O₂ metabolism inhibitors or scavengers. Also, pHBA‐induced NO and H₂O₂ could be compromised in NO synthesis mutants noa1, nia1 and nia2, or H₂O₂ metabolism mutant rbohD/F, but suppressing NO accumulation with a NO synthesis inhibitor or using NO synthesis‐related mutants did not reduce pHBA‐induced H₂O₂ accumulation. Furthermore, we found that the effect of pHBA on allelopathic inhibition of growth was aggravated in NO/H₂O₂ metabolism‐related mutants or reducing NO/H₂O₂ by different inhibitors, whereas the addition of an NO/H₂O₂ donor could partly relieve the inhibitory effect of pHBA on the growth of wild type. However, adding only an NO donor, but not low concentration of H₂O₂ as the donor, could relieve the inhibitory effect of pHBA on root growth in NO metabolism mutants. On the basis of these results, we propose that both NO and H₂O₂ are important signals that mediate Arabidopsis response to the allelopathic chemical pHBA, where during this process H₂O₂ may work upstream of the NO signal.