Integrated Venomics and Venom Gland Transcriptome Analysis of Juvenile and Adult Mexican Rattlesnakes Crotalus simus, C. tzabcan, and C. culminatus Revealed miRNA-modulated Ontogenetic Shifts

• Published in: Journal of proteome research Vol. 16; no. 9; pp. 3370 - 3390
• Main Authors: Durban, Jordi, Sanz, Libia, Trevisan-Silva, Dilza, Neri-Castro, Edgar, Alagón, Alejandro, Calvete, Juan J
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-09-2017
• Subjects: Age Factors; Animals; Base Sequence; Chromatography, Reverse-Phase - methods; Crotalid Venoms - biosynthesis; Crotalid Venoms - classification; Crotalid Venoms - genetics; Crotalid Venoms - isolation & purification; Crotalus - genetics; Crotalus - growth & development; Crotalus - metabolism; Gene Expression Profiling; Gene Expression Regulation; Gene Ontology; Genetic Variation; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular Sequence Annotation; Protein Biosynthesis; Proteogenomics - instrumentation; Proteogenomics - methods; Proteome - genetics; Proteome - metabolism; Species Specificity; Transcriptome; miRNA-mediated post-transcriptional modulation; Mexican rattlesnakes; Crotalus simus; Crotalus tzabcan; venom gland transcriptomics; Crotalus culminatus; venomics; snake venom proteomics; ontogenetic venom shift; venom gland miRNA profiling
• ISSN: 1535-3893; 1535-3907
• DOI: 10.1021/acs.jproteome.7b00414

Adult rattlesnakes within genus Crotalus express one of two distinct venom phenotypes, type I (hemorrhagic) and type II (neurotoxic). In Costa Rican Central American rattlesnake, ontogenetic changes in the concentration of miRNAs modulate venom type II to type I transition. Venomics and venom gland transcriptome analyses showed that adult C. simus and C. tzabcan expressed intermediate patterns between type II and type I venoms, whereas C. culminatus had a canonical type I venom. Neonate/juvenile and adult Mexican rattlesnakes showed notable inter- and intraspecific variability in the number, type, abundance and ontogenetic shifts of the transcriptional and translational venom gland activities. These results support a role for miRNAs in the ontogenetic venom compositional changes in the three congeneric Mexican rattlesnakes. It is worth noting the finding of dual-action miRNAs, which silence the translation of neurotoxic heterodimeric PLA2 crotoxin and acidic PLA2 mRNAs while simultaneously up-regulating SVMP-targeting mRNAs. Dual transcriptional regulation potentially explains the existence of mutually exclusive crotoxin-rich (type-II) and SVMP-rich (type-I) venom phenotypic dichotomy among rattlesnakes. Our results support the hypothesis that alterations of the distribution of miRNAs, modulating the translational activity of venom gland toxin-encoding mRNAs in response to an external cue, may contribute to the mechanism generating adaptive venom variability.