Distinct regulatory networks control toxin gene expression in elapid and viperid snakes.

Autor: Modahl CM; Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, Singapore. Cassandra.Modahl@lstmed.ac.uk.; Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, U.K.. Cassandra.Modahl@lstmed.ac.uk., Han SX; Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, Singapore.; Fulcrum Therapeutics, Cambridge, MA, U.S.A., van Thiel J; Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, U.K.; Institute of Biology Leiden, Leiden University, Leiden, The Netherlands., Vaz C; Human Development, Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Dunstan NL; Venom Supplies, Tanunda, South Australia, Australia., Frietze S; Department of Biomedical and Health Sciences, University of Vermont, Burlington, VT, U.S.A., Jackson TNW; Australian Venom Research Unit, Department of Biochemistry and Pharmacology, University of Melbourne, Melbourne, Australia., Mackessy SP; Department of Biological Sciences, University of Northern Colorado, Greeley, CO, U.S.A., Kini RM; Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, Singapore. dbskinim@nus.edu.sg.; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. dbskinim@nus.edu.sg.; Singapore Eye Research Institute, Singapore, Singapore. dbskinim@nus.edu.sg.; Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA, U.S.A.. dbskinim@nus.edu.sg.
Jazyk: angličtina
Zdroj: BMC genomics [BMC Genomics] 2024 Feb 16; Vol. 25 (1), pp. 186. Date of Electronic Publication: 2024 Feb 16.
DOI: 10.1186/s12864-024-10090-y
Abstrakt: Background: Venom systems are ideal models to study genetic regulatory mechanisms that underpin evolutionary novelty. Snake venom glands are thought to share a common origin, but there are major distinctions between venom toxins from the medically significant snake families Elapidae and Viperidae, and toxin gene regulatory investigations in elapid snakes have been limited. Here, we used high-throughput RNA-sequencing to profile gene expression and microRNAs between active (milked) and resting (unmilked) venom glands in an elapid (Eastern Brown Snake, Pseudonaja textilis), in addition to comparative genomics, to identify cis- and trans-acting regulation of venom production in an elapid in comparison to viperids (Crotalus viridis and C. tigris).
Results: Although there is conservation in high-level mechanistic pathways regulating venom production (unfolded protein response, Notch signaling and cholesterol homeostasis), there are differences in the regulation of histone methylation enzymes, transcription factors, and microRNAs in venom glands from these two snake families. Histone methyltransferases and transcription factor (TF) specificity protein 1 (Sp1) were highly upregulated in the milked elapid venom gland in comparison to the viperids, whereas nuclear factor I (NFI) TFs were upregulated after viperid venom milking. Sp1 and NFI cis-regulatory elements were common to toxin gene promoter regions, but many unique elements were also present between elapid and viperid toxins. The presence of Sp1 binding sites across multiple elapid toxin gene promoter regions that have been experimentally determined to regulate expression, in addition to upregulation of Sp1 after venom milking, suggests this transcription factor is involved in elapid toxin expression. microRNA profiles were distinctive between milked and unmilked venom glands for both snake families, and microRNAs were predicted to target a diversity of toxin transcripts in the elapid P. textilis venom gland, but only snake venom metalloproteinase transcripts in the viperid C. viridis venom gland. These results suggest differences in toxin gene posttranscriptional regulation between the elapid P. textilis and viperid C. viridis.
Conclusions: Our comparative transcriptomic and genomic analyses between toxin genes and isoforms in elapid and viperid snakes suggests independent toxin regulation between these two snake families, demonstrating multiple different regulatory mechanisms underpin a venomous phenotype.
(© 2024. The Author(s).)
Databáze: MEDLINE
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