title: RNA interference screen reveals a high proportion of mitochondrial proteins essential for correct cell cycle progress in Trypanosoma brucei.
abstract: BACKGROUND
  Trypanosomatid parasites possess a single mitochondrion which is classically involved in the energetic metabolism of the cell, but also, in a much more original way, through its single and complex DNA (termed kinetoplast), in the correct progress of cell division. In order to identify proteins potentially involved in the cell cycle, we performed RNAi knockdowns of 101 genes encoding mitochondrial proteins using procyclic cells of Trypanosoma brucei.
  
  
  RESULTS
  A major cell growth reduction was observed in 10 cases and a moderate reduction in 29 other cases. These data are overall in agreement with those previously obtained by a case-by-case approach performed on chromosome 1 genes, and quantitatively with those obtained by "high-throughput phenotyping using parallel sequencing of RNA interference targets" (RIT-seq). Nevertheless, a detailed analysis revealed many qualitative discrepancies with the RIT-seq-based approach. Moreover, for 37 out of 39 mutants for which a moderate or severe growth defect was observed here, we noted abnormalities in the cell cycle progress, leading to increased proportions of abnormal cell cycle stages, such as cells containing more than 2 kinetoplasts (K) and/or more than 2 nuclei (N), and modified proportions of the normal phenotypes (1N1K, 1N2K and 2N2K).
  
  
  CONCLUSIONS
  These data, together with the observation of other abnormal phenotypes, show that all the corresponding mitochondrial proteins are involved, directly or indirectly, in the correct progress or, less likely, in the regulation, of the cell cycle in T. brucei. They also show how post-genomics analyses performed on a case-by-case basis may yield discrepancies with global approaches.
authors.affiliation: Université Montpellier 1, UFR Médecine, Laboratoire de Parasitologie-Mycologie, CHRU de Montpellier, 39, Avenue Charles Flahault, 34295, Montpellier, Cedex 5, France. diane-ethna.benet@univ-montp1.fr.|CNRS 5290 - IRD 224 - Université Montpellier (UMR "MiVEGEC"), Montpellier, France. diane-ethna.benet@univ-montp1.fr.
authors.forename: Diane-Ethna
authors.initials: DE
authors.lastname: Mbang-Benet
authors.affiliation: Université Montpellier 1, UFR Médecine, Laboratoire de Parasitologie-Mycologie, CHRU de Montpellier, 39, Avenue Charles Flahault, 34295, Montpellier, Cedex 5, France. yvon.sterkers@univ-montp1.fr.|CNRS 5290 - IRD 224 - Université Montpellier (UMR "MiVEGEC"), Montpellier, France. yvon.sterkers@univ-montp1.fr.|Département de Parasitologie-Mycologie, CHRU (Centre Hospitalier Universitaire de Montpellier), Montpellier, France. yvon.sterkers@univ-montp1.fr.
authors.forename: Yvon
authors.initials: Y
authors.lastname: Sterkers
authors.affiliation: CNRS 5290 - IRD 224 - Université Montpellier (UMR "MiVEGEC"), Montpellier, France. lucien.crobu@univ-montp1.fr.
authors.forename: Lucien
authors.initials: L
authors.lastname: Crobu
authors.affiliation: Montpellier RIO Imaging Facility, Montpellier BIOCAMPUS, UMS3426, Arnaud de Villeneuve Campus Imaging Facility - Institut de Génétique Humaine-CNRS, Montpellier, France. amelie.sarrazin@igh.cnrs.fr.
authors.forename: Amélie
authors.initials: A
authors.lastname: Sarrazin
authors.affiliation: Université Montpellier 1, UFR Médecine, Laboratoire de Parasitologie-Mycologie, CHRU de Montpellier, 39, Avenue Charles Flahault, 34295, Montpellier, Cedex 5, France. patrick.bastien@univ-montp1.fr.|CNRS 5290 - IRD 224 - Université Montpellier (UMR "MiVEGEC"), Montpellier, France. patrick.bastien@univ-montp1.fr.|Département de Parasitologie-Mycologie, CHRU (Centre Hospitalier Universitaire de Montpellier), Montpellier, France. patrick.bastien@univ-montp1.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bastien
authors.affiliation: Université Montpellier 1, UFR Médecine, Laboratoire de Parasitologie-Mycologie, CHRU de Montpellier, 39, Avenue Charles Flahault, 34295, Montpellier, Cedex 5, France. gpp@univ-montp1.fr.|CNRS 5290 - IRD 224 - Université Montpellier (UMR "MiVEGEC"), Montpellier, France. gpp@univ-montp1.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Pagès
mesh_terms: D002455:Cell Division / Q000502:physiology; D048749:Cytokinesis / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009841:Oligonucleotides / Q000378:metabolism; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D014346:Trypanosoma brucei brucei / Q000254:growth & development / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D009841:Oligonucleotides; D015800:Protozoan Proteins