Wagh, P. R. | Search bioRxiv

bioRxiv2026

The gene ivory:mir-193 controls scale type differentiation in Heliconius butterflies

The ivory:mir-193 locus is a genetic hotspot underlying melanic wing pattern variation across Lepidoptera, acting as a master regulator of melanic scale fate. This includes the genus Heliconius, where aposematic mimicry is driven by three scale cell types: light Type I, dark-melanic Type II, and red Type III scales. We tested functions of ivory:mir-193 in Heliconius using CRISPR-induced somatic mosaic knockouts of ivory and mir-193 across multiple pattern morphs. Knockouts converted Type II scales to Type I scales. Effects on Type III scales varied among and within individuals, indicating that ivory:mir-193 is permissive for Type III development. Using single-nucleus RNA-seq, we profiled the transcriptional landscape of H. melpomene-{Delta}78k mutants lacking mir-193. Loss of mir-193 produced readthrough transcription, consistent with a model where miR-193 acts as a co-transcriptional terminator. These data show that ivory drives wing pattern variation, while mir-193 mediates downstream diversity in scale fate across Lepidoptera.

evolutionary biology↗

bioRxiv2020

Immunoproteasome impairment via β5i/LMP7-deletion leads to sustained pancreatic injury and delayed recovery from experimental pancreatitis.

Background & AimsUncovering potential new targets involved in pancreas recovery may permit the development of new therapies and improvement of pancreatitis treatment. One disease mechanism comprises the endoplasmic reticulum stress response and a key regulator to prevent proteotoxic stress in an inflammatory context is the immunoproteasome, an induced form of the constitutive proteasome. Our aim was therefore to investigate the role of the immunoproteasome in acute pancreatitis. MethodsAcute pancreatitis was induced in wild type and LMP7-/- mice and several biochemical parameters for disease severity were addressed, including protease activities and histology of pancreatic damage. Real-time PCR was used to measure pro-inflammation and unfolded protein response. Serum IL-6 was detected by cytometric bead assay. Western blotting was used to quantify the ratio of ubiquitin-protein conjugates as well as unfolded protein response activation. Immunofluorescence identified leukocytes infiltration as well as ubiquitin-protein conjugates in the pancreas. ResultsIn this study, we demonstrate that the {beta}5i/LMP7-subunit deletion correlates with persistent pancreatic damage. Interestingly, immunoproteasome-deficient mice unveil increased activity of pancreatic enzymes as well as higher secretion of Interleukin-6 and transcript expression of the Interleukin IL-1{beta}, IFN-{beta} cytokines and the CXCL-10 chemokine. Thereafter, acinar cell death was increased, which appears to be due to the greater accumulation of ubiquitin-protein conjugates and prolonged unfolded protein response. ConclusionsOur findings suggest that the immunoproteasome plays a protective role in acute pancreatitis via its role in the clearance of damaged proteins and the balance of ER-stress responses in pancreatic acini as well as in macrophages cytokine production.

physiology↗