Two cold shock domain containing proteins trigger the development of infectious Trypanosoma brucei. 2023

Justin Y Toh, and Agathe Nkouawa, and Gang Dong, and Nikolay G Kolev, and Christian Tschudi
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.

Cold shock proteins are members of a family of DNA- and RNA-binding proteins with one or more evolutionarily conserved cold shock domain (CSD). These proteins have a wide variety of biological functions, including DNA-damage repair, mRNA stability, and regulation of transcription, splicing and translation. We previously identified two CSD containing proteins, CSD1 and CSD2, in the protozoan parasite Trypanosoma brucei to be required for RBP6-driven metacyclic production, albeit at different steps of the developmental program. During metacyclogenesis T. brucei undergoes major morphological and metabolic changes that culminate in the establishment of quiescent metacyclic parasites and the acquisition of mammalian infectivity. To investigate the specific role of CSD1 and CSD2 in this process, we ectopically expressed CSD1 or CSD2 in non-infectious procyclic parasites and discovered that each protein is sufficient to produce infectious metacyclic parasites in 24 hours. Domain truncation assays determined that the N-terminal domain, but not the C-terminal domain, of CSD1 and CSD2 was required for metacyclic development. Furthermore, conserved amino acid residues in the CSD of CSD1 and CSD2, known to be important for binding nucleic acids, were found to be necessary for metacyclic production. Using single-end enhanced crosslinking and immunoprecipitation (seCLIP) we identified the specific binding motif of CSD1 and CSD2 as "ANACAU" and the bound mRNAs were enriched for biological processes, including lipid metabolism, microtubule-based movement and nucleocytoplasmic transport that are likely involved in the transition to bloodstream form-like cells.

UI MeSH Term Description Entries
D008322 Mammals Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young. Mammalia,Mammal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014346 Trypanosoma brucei brucei A hemoflagellate subspecies of parasitic protozoa that causes nagana in domestic and game animals in Africa. It apparently does not infect humans. It is transmitted by bites of tsetse flies (Glossina). Trypanosoma brucei,Trypanosoma brucei bruceus,Trypanosoma bruceus,brucei brucei, Trypanosoma,brucei, Trypanosoma brucei,bruceus, Trypanosoma,bruceus, Trypanosoma brucei
D015800 Protozoan Proteins Proteins found in any species of protozoan. Proteins, Protozoan
D016601 RNA-Binding Proteins Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA. Double-Stranded RNA-Binding Protein,Double-Stranded RNA-Binding Proteins,ds RNA-Binding Protein,RNA-Binding Protein,ds RNA-Binding Proteins,Double Stranded RNA Binding Protein,Double Stranded RNA Binding Proteins,Protein, Double-Stranded RNA-Binding,Protein, ds RNA-Binding,RNA Binding Protein,RNA Binding Proteins,RNA-Binding Protein, Double-Stranded,RNA-Binding Protein, ds,RNA-Binding Proteins, Double-Stranded,ds RNA Binding Protein
D057773 Cold Shock Proteins and Peptides Cellular proteins and peptides that are induced in response to cold stress. They are found in a broad variety of prokaryotic and eukaryotic organisms. Cold Shock Peptide,Cold Shock Protein,Cold Stress Peptide,Cold Stress Protein,Cold Shock Peptides,Cold Shock Proteins,Cold Stress Peptides,Cold Stress Proteins,Cold Stress Proteins and Peptides,Peptide, Cold Shock,Peptide, Cold Stress,Protein, Cold Shock,Protein, Cold Stress,Shock Peptide, Cold,Shock Peptides, Cold,Shock Protein, Cold,Shock Proteins, Cold,Stress Peptide, Cold,Stress Peptides, Cold,Stress Protein, Cold,Stress Proteins, Cold
D058639 Cold-Shock Response A sequence of responses that occur when an organism is exposed to excessive cold. In humans, a fall in skin temperature triggers gasping, hypertension, and hyperventilation. Cold Shock,Cold Shock Stress,Cold Stress,Cold-Stress Reaction,Cold-Stress Response,Cold Shock Response,Cold Shock Stresses,Cold Shocks,Cold Stress Reaction,Cold Stress Response,Cold-Shock Responses,Cold-Stress Reactions,Cold-Stress Responses,Response, Cold-Stress,Responses, Cold-Stress,Shock Stress, Cold,Shock Stresses, Cold,Stress, Cold,Stress, Cold Shock,Stresses, Cold Shock

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