A novel, essential trans-splicing protein connects the nematode SL1 snRNP to the CBC-ARS2 complex.

Spliced leader trans-splicing is essential for gene expression in many eukaryotes. To elucidate the molecular mechanism of this process, we characterise the molecules associated with the Caenorhabditis elegans major spliced leader snRNP (SL1 snRNP), which donates the spliced leader that replaces the 5' untranslated region of most pre-mRNAs. Using a GFP-tagged version of the SL1 snRNP protein SNA-1 created by CRISPR-mediated genome engineering, we immunoprecipitate and identify RNAs and protein components by RIP-Seq and mass spectrometry. This reveals the composition of the SL1 snRNP and identifies associations with spliceosome components PRP-8 and PRP-19. Significantly, we identify a novel, nematode-specific protein required for SL1 trans-splicing, which we designate SNA-3. SNA-3 is an essential, nuclear protein with three NADAR domains whose function is unknown. Mutation of key residues in NADAR domains inactivates the protein, indicating that domain function is required for activity. SNA-3 interacts with the CBC-ARS2 complex and other factors involved in RNA metabolism, including SUT-1 protein, through RNA or protein-mediated contacts revealed by yeast two-hybrid assays, localisation studies and immunoprecipitations. Our data are compatible with a role for SNA-3 in coordinating trans-splicing with target pre-mRNA transcription or in the processing of the Y-branch product of the trans-splicing reaction.

The antiplasmodial activity of Anogeissus leiocarpus and its effect on oxidative stress and lipid profile in mice infected with Plasmodium bergheii.

Methanolic extracts of Anogeissus leiocarpus has been considered locally to have the same antimalarial activities as artemisinin derivatives. This work studied the in vivo antiplasmodial activity of methanolic extracts of A. leiocarpus and its effect on oxidative stress and lipid profile in mice infected with Plasmodium bergheii. Mice used for this study were divided into five groups; four of the groups were infected with P. bergheii. The first group was not infected with the parasite. The second group was infected with parasite but not treated with antimalarial drugs (negative control). The third group was infected and treated with artesunat at 5 mg/kg body weight (positive control), while the fourth and fifth groups were infected and treated with 100 and 200 mg/kg body weight of extract of stem bark of A. leiocarpus, respectively. The rate of parasite clearance was higher in the group treated with 200 mg/kg body weight of extract of A. leiocarpus when compared with the groups treated with artesunat. Malondialdehyde (MDA) level was significantly higher (P < 0.05) in the serum of negative control as compared with other groups which have received treatment. MDA level was moderately higher in the liver homogenates of infected mice treated with artesunat than in other groups. There were significant increases (P < 0.05) in the levels of serum and liver superoxide dismutase of infected mice treated with 200 mg/kg body weight of A. leiocarpus when compared with other groups. Serum low density lipoprotein, total triglyceride, and total cholesterol were moderately higher in the group treated with artesunat than other groups, while high density lipoprotein (HDL) level was higher in the two groups treated with A. leiocarpus as compared with the group treated with artesunat. This study shows that the methanolic extract of A. leiocarpus has high antimalarial activities, high antioxidant property, and capable of boosting HDL level in malaria-infected organisms.