DHX9/DNA-tandem repeat-dependent downregulation of ciRNA-Fmn1 in the dorsal horn is required for neuropathic pain.

Circular RNAs (ciRNAs) are emerging as new players in the regulation of gene expression. However, how ciRNAs are involved in neuropathic pain is poorly understood. Here, we identify the nervous-tissue-specific ciRNA-Fmn1 and report that changes in ciRNA-Fmn1 expression in spinal cord dorsal horn neurons play a key role in neuropathic pain after nerve injury. ciRNA-Fmn1 was significantly downregulated in ipsilateral dorsal horn neurons after peripheral nerve injury, at least in part because of a decrease in DNA helicase 9 (DHX9), which regulates production of ciRNA-Fmn1 by binding to DNA-tandem repeats. Blocking ciRNA-Fmn1 downregulation reversed nerve-injury-induced reductions in both the binding of ciRNA-Fmn1 to the ubiquitin ligase UBR5 and the level of ubiquitination of albumin (ALB), thereby abrogating the nerve-injury-induced increase of ALB expression in the dorsal horn and attenuating the associated pain hypersensitivities. Conversely, mimicking downregulation of ciRNA-Fmn1 in naïve mice reduced the UBR5-controlled ubiquitination of ALB, leading to increased expression of ALB in the dorsal horn and induction of neuropathic-pain-like behaviors in naïve mice. Thus, ciRNA-Fmn1 downregulation caused by changes in binding of DHX9 to DNA-tandem repeats contributes to the genesis of neuropathic pain by negatively modulating UBR5-controlled ALB expression in the dorsal horn.

Infection of the entomopathogenic fungus Metarhizium rileyi suppresses cellular immunity and activates humoral antibacterial immunity of the host Spodoptera frugiperda.

BACKGROUND: Metarhizium rileyi is an entomopathogenic fungus with promising potential for controlling agricultural pests, including Spodoptera frugiperda. Following penetration of the host through the cuticle, M. rileyi cells transform into in vivo blastospores or hyphal bodies, propagating within the hemocoel. However, the strategies and molecular mechanisms by which M. rileyi survives upon exposure to the powerful insect immune system remain unclear. RESULTS: We determined the pathogenicity of M. rileyi and found that either conidial immersion or blastospore injection significantly decreased S. frugiperda survival in a dose-dependent manner. Injection of M. rileyi blastospores decreased the number of S. frugiperda hemocytes and impaired host cellular reactions such as nodulation, encapsulation and phagocytosis. Blastospore injection led to increased antibacterial activity in plasma at 48 h post-injection (hpi). RNA-sequencing analyses identified a large number of antimicrobial peptide genes upregulated in the fat body of M. rileyi-infected larvae at 48 hpi, which may be attributable to the activation of Toll and IMD signaling pathway. CONCLUSION: This study demonstrates that the compromised cellular immunity of the insect host is due to the marked decrease in hemocytes and impaired cellular cytoskeletons, which may facilitate early infection by M. rileyi. Late in the course of infection, the enhanced antibacterial activity of plasma, which may be in response to intestinal evading bacteria, cannot inhibit hyphal growth in hemolymph. Our data provide a comprehensive resource for exploring the molecular mechanism employed by M. rileyi to overcome S. frugiperda immunity. © 2022 Society of Chemical Industry.