🧬 PubMed RNA Editing Daily Digest

Gene drives are engineered alleles that bias their own inheritance in offspring, enabling the spread of specific traits throughout a population. Targeting female fertility genes in a gene drive can be an efficient strategy for population suppression. In this study, we investigated nine female fertility genes in Drosophila melanogaster using CRISPR-based homing gene drives. Employing a multiplexed gRNA approach to prevent the formation of functional resistance alleles, we aimed to maintain high drive-conversion efficiency with low fitness costs in female drive-carriers. Drive efficiency was assessed in individual crosses and had varied performance across different target genes. Notably, drives targeting the octopamine β2 receptor (oct) and stall (stl) genes exhibited the highest drive-conversion rates and were further tested in cages. A drive targeting stl successfully suppressed a cage population with a high release frequency, though suppression failed in another replicate cage with a lower initial release frequency. Fitness costs in female drive carriers were observed in test cages, impacting the overall efficiency of population suppression. Further tests on the fertility of these lines using individual crosses indicated that some fitness costs were due to maternal deposition of Cas9 combined with new gRNA expression, which would only occur in progeny of drive males when testing split drives with separate Cas9 (when mimicking cages with complete drives) but not for complete drive systems. This could enable success in complete drives with higher maternal Cas9 deposition, even if cage experiments in split drives fail. Overall, our findings identify oct and stl as promising fertility targets and demonstrate both the potential and the constraints of fertility-based suppression drives, providing empirical evidence to guide the design and assessment of more efficient population control strategies.

Lygus lineolaris and Lygus hesperus are economically important pests that cause substantial damage to wide variety of crops in the United States. In this study, we isolated 17 full-length voltage-gated sodium channels cDNA clones encoding 14 unique splicing variants from a susceptible strain of L. hesperus (sLhNav), two variants from a susceptible L. lineolaris strain (sLlNav), and 8 clones encoding 7 variants from a pyrethroid-resistant L. lineolaris population (rLlNav), based on the usage of 12 alternative exons. Functional expression in Xenopus oocytes revealed that 11 sLh/LlNav variants produced sodium currents suitable for electrophysiological analysis, which displayed distinct gating properties. Notably, Nav variants lacking exon b generated significantly larger currents compared to those including exon b. We also identified A-to-I editing events in both Lygus Navs, and a key finding was the identification of three kdr mutations in rLlNav variants, L1023 F/S in segment IIS6 and L934I in the IIS4-S5 linker (corresponding to L1014F, L1014S and L925I in housefly Nav), all of which have been previously associated with pyrethroid resistance in other insect species. This is the first report of these mutations in resistant L. lineolaris populations. Together with earlier reports of enhanced metabolic detoxification, our findings suggest a dual resistance strategy in L. lineolaris, involving both target-site insensitivity and elevated detoxification enzyme activity. The comprehensive characterization of sodium channel variants in both Lygus, along with the identification of L1023 F/S and L934I mutations, provides valuable insight into Nav diversity in Lygus species and the molecular basis of pyrethroid resistance in L. lineolaris.

Achieving pancreatic-targeted delivery marks a breakthrough in treating pancreatic diseases, yet precise delivery remains challenging

Bats, often silent carriers of lethal pathogens, serve as natural reservoirs for numerous viruses capable of crossing species barriers with devastating effects. Among them, Rousettus aegyptiacus (R. aegyptiacus) has emerged as a pivotal species in understanding viral spillovers. This fruit bat hosts the Marburg virus (MARV), supporting its replication and occasional transmission to humans, where it causes fatal hemorrhagic fever. However, a striking paradox remains while MARV infection is deadly in humans, R. aegyptiacus remains asymptomatic. Driven by this contrast, our study explores the codon usage patterns to reveal evolutionary mechanisms underlying viral adaptation and host tolerance. Far from being a passive carrier, R. aegyptiacus represents an insightful model for antiviral research. Our analysis revealed distinct codon usage patterns in MARV, indicating fine-tuned evolutionary alignment with the host's codon preferences. MARV exhibited low codon bias, suggesting broad compatibility with the host's translational machinery. Further, COA and PR2 analyses suggested that ecological factors shape codon selection in both virus and host. RNA modification analysis revealed frequent cytosine-to-thymine transitions, implying conserved mutational pressures or host-driven editing. Variations in RCDI values indicated deoptimized codon usage.