Fan, H.-C. | Search bioRxiv

bioRxiv2023

Phase transition of maternal RNAs during vertebrate oocyte-to-embryo transition

The oocyte-to-embryo transition (OET) is regulated by maternal products stored in the oocyte cytoplasm, independent of transcription. How maternal products are precisely remodeled to dictate the OET remains an open question. In this work, we discover the dynamic phase transition of maternal RNAs during Xenopus OET. We have identified 863 maternal transcripts that transition from a soluble state to a detergent-insoluble one after oocyte maturation. These RNAs are enriched in the animal hemisphere and many of them encode key cell cycle regulators. In contrast, 165 transcripts, including nearly all Xenopus germline RNAs and some vegetally localized somatic RNAs, undergo an insoluble-to-soluble phase transition. This phenomenon is conserved in zebrafish. Our results demonstrate that the phase transition of germline RNAs influences their susceptibility to RNA degradation machinery and is mediated by the remodeling of germ plasm. This work thus uncovers novel remodeling mechanisms that act on RNAs to regulate vertebrate OET.

developmental biology↗

bioRxiv2022

Aldo-Keto Reductase Family 1 Member A1 (AKR1A1) Deficiency Exacerbates Alcohol-Induced Hepatic Oxidative Stress, Inflammation, Steatosis, and Fibrosis

BackgroundAlcohol-associated liver disease (ALD) covers a wide range of hepatic lesions that depend on the amount and duration of alcohol consumption, from early and reversible conditions to hepatic steatosis and severe lesions, including steatohepatitis and alcoholic fibrosis, to irreversible cirrhosis. AKR1A1, an aldo-keto reductase family member, participates in the detoxification of alcohol-derived acetaldehyde, but its role in ALD remains unclear. In this study, we studied the role of AKR1A1 in the development of ALD using Akr1a1-/- knockout mice and palmitic acid/oleic acid (P/O) plus ethanol-treated AML12 hepatocyte cells. MethodsLevels of AKR1A1 were measured in mice fed with the Lieber-DeCarli diet containing 5% alcohol (alcohol-fed, AF) or control liquid diet (pair-fed, PF). The effects of AKR1A1 on the liver function, inflammation, oxidative stress, lipid accumulation, and fibrosis were assessed in AF-induced Akr1a1-/- and ICR control mice. ResultsData showed that AF-Akr1a1-/- mice exhibited an exacerbation of liver injury and increased gene and protein levels of inflammatory mediators, oxidative stress, lipid accumulation, and fibrosis, whilst decreased expression of antioxidant enzymes in their livers than the AF-ICR mice. Therefore, loss of AKR1A1 can activate 4-HNE/p53 signaling to modulate ROS and antioxidant balance, increase lipid peroxidation, fatty acid synthesis and lipid droplet formation, reduced fatty acid {beta}-oxidation, and elevated proinflammatory and fibrotic mediator, eventually exacerbate the ALD. In in vitro study, we further demonstrated that knockdown of Akrlal aggravated the effects of alcohol plus P/O-induced oxidative stress and steatosis, LPS-stimulated inflammation, and TGF-{beta}1-induced fibrosis in AML12 hepatocyte cells. Conclusionour results revealed that AKR1A1 exerts protective effects on alcohol-induced liver injury, steatosis, and fibrosis, possibly by regulating the 4-HNE-p53 signaling pathway.

pathology↗