title: A pseudouridylation switch in rRNA is implicated in ribosome function during the life cycle of Trypanosoma brucei.
abstract: The protozoan parasite Trypanosoma brucei, which causes devastating diseases in humans and animals in sub-Saharan Africa, undergoes a complex life cycle between the mammalian host and the blood-feeding tsetse fly vector. However, little is known about how the parasite performs most molecular functions in such different environments. Here, we provide evidence for the intriguing possibility that pseudouridylation of rRNA plays an important role in the capacity of the parasite to transit between the insect midgut and the mammalian bloodstream. Briefly, we mapped pseudouridines (Ψ) on rRNA by Ψ-seq in procyclic form (PCF) and bloodstream form (BSF) trypanosomes. We detected 68 Ψs on rRNA, which are guided by H/ACA small nucleolar RNAs (snoRNA). The small RNome of both life cycle stages was determined by HiSeq and 83 H/ACAs were identified. We observed an elevation of 21 Ψs modifications in BSF as a result of increased levels of the guiding snoRNAs. Overexpression of snoRNAs guiding modification on H69 provided a slight growth advantage to PCF parasites at 30 °C. Interestingly, these modifications are predicted to significantly alter the secondary structure of the large subunit (LSU) rRNA suggesting that hypermodified positions may contribute to the adaption of ribosome function during cycling between the two hosts.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900 Israel.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Chikne
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900 Israel.
authors.forename: Tirza
authors.initials: T
authors.lastname: Doniger
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900 Israel.
authors.forename: K Shanmugha
authors.initials: KS
authors.lastname: Rajan
authors.affiliation: Department of Biological Chemistry, The Alexander Silberman Inst. of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel.
authors.forename: Osnat
authors.initials: O
authors.lastname: Bartok
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900 Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Eliaz
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900 Israel.
authors.forename: Smadar
authors.initials: S
authors.lastname: Cohen-Chalamish
authors.affiliation: Department of Epidemiology and Microbial Diseases, Yale School of Public Health, New Haven, CT 06536, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Tschudi
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900 Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Unger
authors.affiliation: Architecture et Réactivité de l'ARN UPR9002, Université de Strasbourg, 67084 Strasbourg, France.
authors.forename: Yaser
authors.initials: Y
authors.lastname: Hashem
authors.affiliation: Department of Biological Chemistry, The Alexander Silberman Inst. of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kadener
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900 Israel.
authors.forename: Shulamit
authors.initials: S
authors.lastname: Michaeli
mesh_terms: D000222:Adaptation, Physiological; D020869:Gene Expression Profiling; D008018:Life Cycle Stages; D011560:Pseudouridine / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000378:metabolism*; D020537:RNA, Small Nucleolar / Q000737:chemistry; D012270:Ribosomes / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D014346:Trypanosoma brucei brucei / Q000502:physiology*
chemical_list: D012335:RNA, Ribosomal; D020537:RNA, Small Nucleolar; D011560:Pseudouridine