Finkielstein, C. v. | bioRxiv Science

bioRxiv2022

Wildlife exposure to SARS-CoV-2 across a human use gradient

Pervasive SARS-CoV-2 infections in humans have led to multiple transmission events to captive animals. While SARS-CoV-2 has a potential broad wildlife host range, most documented infections to date are found in a single species, the white-tailed deer. The extent of SARS-CoV-2 exposure among wildlife species and the factors that influence wildlife transmission risk remain unknown. We sampled 23 wildlife species for SARS-CoV-2 and examined the effects of urbanization and human use on seropositivity. Here, we document positive detections of SARS-CoV-2 RNA in six species, including the deer mouse, Virginia opossum, raccoon, groundhog, Eastern cottontail, and Eastern red bat. In addition, we found that sites with high human activity had three times higher seroprevalence than low human-use areas. We detected SARS-CoV-2 genomic sequences from nine individuals of six species which were assigned to seven Pango lineages of the Omicron variant. The close match to variants circulating in humans at the time suggests at least seven recent human-to-animal transmission events. Our data support that exposure to SARS-CoV-2 has been widespread in wildlife communities and suggests that areas with high human activity may serve as points of contact for cross-species transmission.

ecology↗

bioRxiv2018

Distinct control of PERIOD2 degradation and circadian rhythms by the oncoprotein MDM2

The circadian clock relies on post-translational modifications to set the timing for degradation of core regulatory components and, thus, sets clock progression. Ubiquitin-modifying enzymes targeting clock components for degradation are known to mostly recognize phosphorylated substrates. A case in point is the circadian factor PERIOD 2 (PER2) whose phospho-specific turnover involves its recognition by {beta}-transducin repeat containing proteins ({beta}-TrCPs). Yet, the existence of this unique mode of regulation of PER2s stability falls short of explaining persistent oscillatory phenotypes reported in biological systems lacking functional elements of the phospho-dependent PER2 degradation machinery.\n\nIn this study, we challenge the phosphorylation-centric view that PER2 degradation enhances circadian rhythm robustness by i) identifying the PER2:MDM2 endogenous complex, ii) establishing PER2 as a previously uncharacterized substrate for MDM2, iii) revealing an alternative phosphorylation-independent mechanism for PER2 ubiquitin-mediated degradation, iv) pinpointing residues for ubiquitin modification, and v) establishing the importance of MDM2-mediated PER2 turnover for defining the circadian period length. Our results not only expand MDM2s suite of specific substrates beyond the cell cycle to include circadian components but also uncover novel regulatory players that likely impact our view of how other mechanisms crosstalk and modulate the clock itself.

molecular biology↗