Trypanosoma brucei spp. cause African human and animal trypanosomiasis, a burden on health and economy in Africa. These hemoflagellates are distinguished by a kinetoplast nucleoid containing mitochondrial DNAs of two kinds: maxicircles encoding ribosomal RNAs (rRNAs) and proteins and minicircles bearing guide RNAs (gRNAs) for mRNA editing. All RNAs are produced by a phage-type RNA polymerase as 3' extended precursors, which undergo exonucleolytic trimming. Most pre-mRNAs proceed through 3' adenylation, uridine insertion/deletion editing, and 3' A/U-tailing. The rRNAs and gRNAs are 3' uridylated. Historically, RNA editing has attracted major research effort, and recently essential pre- and postediting processing events have been discovered. Here, we classify the key players that transform primary transcripts into mature molecules and regulate their function and turnover.

• Klíčová slova
• RNA decay, RNA editing, Trypanosoma, kinetoplast, mitochondria, polyadenylation,
• MeSH
• editace RNA fyziologie   MeSH
• RNA mitochondriální genetika   metabolismus   MeSH
• RNA protozoální genetika   metabolismus   MeSH
• Trypanosoma brucei brucei genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• RNA mitochondriální MeSH
• RNA protozoální MeSH

Genome-wide studies of African populations have the potential to reveal powerful insights into the evolution of our species, as these diverse populations have been exposed to intense selective pressures imposed by infectious diseases, diet, and environmental factors. Within Africa, the Sahel Belt extensively overlaps the geographical center of several endemic infections such as malaria, trypanosomiasis, meningitis, and hemorrhagic fevers. We screened 2.5 million single nucleotide polymorphisms in 161 individuals from 13 Sahelian populations, which together with published data cover Western, Central, and Eastern Sahel, and include both nomadic and sedentary groups. We confirmed the role of this Belt as a main corridor for human migrations across the continent. Strong admixture was observed in both Central and Eastern Sahelian populations, with North Africans and Near Eastern/Arabians, respectively, but it was inexistent in Western Sahelian populations. Genome-wide local ancestry inference in admixed Sahelian populations revealed several candidate regions that were significantly enriched for non-autochthonous haplotypes, and many showed to be under positive selection. The DARC gene region in Arabs and Nubians was enriched for African ancestry, whereas the RAB3GAP1/LCT/MCM6 region in Oromo, the TAS2R gene family in Fulani, and the ALMS1/NAT8 in Turkana and Samburu were enriched for non-African ancestry. Signals of positive selection varied in terms of geographic amplitude. Some genomic regions were selected across the Belt, the most striking example being the malaria-related DARC gene. Others were Western-specific (oxytocin, calcium, and heart pathways), Eastern-specific (lipid pathways), or even population-restricted (TAS2R genes in Fulani, which may reflect sexual selection).

• Klíčová slova
• Sahel, admixture, genome-wide diversity, selection,
• MeSH
• acetyltransferasy genetika   MeSH
• genom lidský * MeSH
• haplotypy MeSH
• hemoragické horečky virové genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• krevní skupiny - systém Duffy genetika   MeSH
• lidé MeSH
• malárie genetika   MeSH
• MCM komplex, komponenta 6 genetika   MeSH
• meningitida genetika   MeSH
• migrace lidstva * MeSH
• proteiny buněčného cyklu MeSH
• proteiny genetika   MeSH
• receptory buněčného povrchu genetika   MeSH
• receptory spřažené s G-proteiny genetika   MeSH
• selekce (genetika) * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Afrika MeSH
• Názvy látek
• acetyltransferasy MeSH
• ACKR1 protein, human MeSH Prohlížeč
• ALMS1 protein, human MeSH Prohlížeč
• krevní skupiny - systém Duffy MeSH
• MCM komplex, komponenta 6 MeSH
• MCM6 protein, human MeSH Prohlížeč
• NAT8 protein, human MeSH Prohlížeč
• proteiny buněčného cyklu MeSH
• proteiny MeSH
• receptory buněčného povrchu MeSH
• receptory spřažené s G-proteiny MeSH
• TAS2R1 protein, human MeSH Prohlížeč

In the infectious stage of Trypanosoma brucei, an important parasite of humans and livestock, the mitochondrial (mt) membrane potential (Δψm) is uniquely maintained by the ATP hydrolytic activity and subsequent proton pumping of the essential FoF1-ATPase. Intriguingly, this multiprotein complex contains several trypanosome-specific subunits of unknown function. Here, we demonstrate that one of the largest novel subunits, ATPaseTb2, is membrane-bound and localizes with monomeric and multimeric assemblies of the FoF1-ATPase. Moreover, RNAi silencing of ATPaseTb2 quickly leads to a significant decrease of the Δψm that manifests as a decreased growth phenotype, indicating that the FoF1-ATPase is impaired. To further explore the function of this protein, we employed a trypanosoma strain that lacks mtDNA (dyskinetoplastic, Dk) and thus subunit a, an essential component of the proton pore in the membrane Fo-moiety. These Dk cells generate the Δψm by combining the hydrolytic activity of the matrix-facing F1-ATPase and the electrogenic exchange of ATP4- for ADP3- by the ATP/ADP carrier (AAC). Surprisingly, in addition to the expected presence of F1-ATPase, the monomeric and multimeric FoF1-ATPase complexes were identified. In fact, the immunoprecipitation of a F1-ATPase subunit demonstrated that ATPaseTb2 was a component of these complexes. Furthermore, RNAi studies established that the membrane-bound ATPaseTb2 subunit is essential for maintaining normal growth and the Δψm of Dk cells. Thus, even in the absence of subunit a, a portion of the FoF1-ATPase is assembled in Dk cells.

• MeSH
• geneticky modifikované organismy MeSH
• kultivované buňky MeSH
• lidé MeSH
• membránové proteiny fyziologie   MeSH
• mitochondriální DNA genetika   MeSH
• mitochondrie genetika   metabolismus   MeSH
• podjednotky proteinů fyziologie   MeSH
• protonové ATPasy fyziologie   MeSH
• skot MeSH
• Trypanosoma brucei brucei * genetika   metabolismus   patogenita   ultrastruktura   MeSH
• trypanozomóza africká krev   parazitologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• membránové proteiny MeSH
• mitochondriální DNA MeSH
• podjednotky proteinů MeSH
• protonové ATPasy MeSH