title: Ribosome profiling reveals translation control as a key mechanism generating differential gene expression in Trypanosoma cruzi.
abstract: BACKGROUND
  Due to the absence of transcription initiation regulation of protein coding genes transcribed by RNA polymerase II, posttranscriptional regulation is responsible for the majority of gene expression changes in trypanosomatids. Therefore, cataloging the abundance of mRNAs (transcriptome) and the level of their translation (translatome) is a key step to understand control of gene expression in these organisms.
  
  
  RESULTS
  Here we assess the extent of regulation of the transcriptome and the translatome in the Chagas disease causing agent, Trypanosoma cruzi, in both the non-infective (epimastigote) and infective (metacyclic trypomastigote) insect's life stages using RNA-seq and ribosome profiling. The observed steady state transcript levels support constitutive transcription and maturation implying the existence of distinctive posttranscriptional regulatory mechanisms controlling gene expression levels at those parasite stages. Meanwhile, the downregulation of a large proportion of the translatome indicates a key role of translation control in differentiation into the infective form. The previously described proteomic data correlate better with the translatomes than with the transcriptomes and translational efficiency analysis shows a wide dynamic range, reinforcing the importance of translatability as a regulatory step. Translation efficiencies for protein families like ribosomal components are diminished while translation of the transialidase virulence factors is upregulated in the quiescent infective metacyclic trypomastigote stage.
  
  
  CONCLUSIONS
  A large subset of genes is modulated at the translation level in two different stages of Trypanosoma cruzi life cycle. Translation upregulation of virulence factors and downregulation of ribosomal proteins indicates different degrees of control operating to prepare the parasite for an infective life form. Taking together our results show that translational regulation, in addition to regulation of steady state level of mRNA, is a major factor playing a role during the parasite differentiation.
authors.affiliation: Laboratory of Molecular Interactions, School of Sciences, Universidad de la República, Montevideo, Uruguay. psmircich@fcien.edu.uy.|Department of Genetics. School of Medicine, Universidad de la República, Montevideo, Uruguay. psmircich@fcien.edu.uy.
authors.forename: Pablo
authors.initials: P
authors.lastname: Smircich
authors.affiliation: Department of Genomics, Instituto de Investigaciones Biológicas Clemente Estable, Av. Italia 3318, Montevideo, CP 11600, Uruguay. geastman@iibce.edu.uy.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Eastman
authors.affiliation: Laboratory of Gene Expression Regulation Studies Carlos Chagas Institute, FIOCRUZ, Curitiba, 81350-010, Brazil. saloebispo@gmail.com.
authors.forename: Saloe
authors.initials: S
authors.lastname: Bispo
authors.affiliation: Laboratory of Molecular Interactions, School of Sciences, Universidad de la República, Montevideo, Uruguay. mduhagon@fcien.edu.uy.|Department of Genetics. School of Medicine, Universidad de la República, Montevideo, Uruguay. mduhagon@fcien.edu.uy.
authors.forename: María Ana
authors.initials: MA
authors.lastname: Duhagon
authors.affiliation: Laboratory of Gene Expression Regulation Studies Carlos Chagas Institute, FIOCRUZ, Curitiba, 81350-010, Brazil. epgslompo@tecpar.br.
authors.forename: Eloise P
authors.initials: EP
authors.lastname: Guerra-Slompo
authors.affiliation: Laboratory of Molecular Interactions, School of Sciences, Universidad de la República, Montevideo, Uruguay. bgarat@fcien.edu.uy.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Garat
authors.affiliation: Laboratory of Gene Expression Regulation Studies Carlos Chagas Institute, FIOCRUZ, Curitiba, 81350-010, Brazil. sgoldenberg@fiocruz.br.
authors.forename: Samuel
authors.initials: S
authors.lastname: Goldenberg
authors.affiliation: Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA. munroed2@mail.nih.gov.
authors.forename: David J
authors.initials: DJ
authors.lastname: Munroe
authors.affiliation: Laboratory of Gene Expression Regulation Studies Carlos Chagas Institute, FIOCRUZ, Curitiba, 81350-010, Brazil. brunod@tecpar.br.
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallagiovanna
authors.affiliation: Laboratory of Gene Expression Regulation Studies Carlos Chagas Institute, FIOCRUZ, Curitiba, 81350-010, Brazil. holetz@fiocruz.br.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Holetz
authors.affiliation: Department of Genomics, Instituto de Investigaciones Biológicas Clemente Estable, Av. Italia 3318, Montevideo, CP 11600, Uruguay. jsotelosilveira@iibce.edu.uy.|Department of Cell and Molecular Biology, School of Sciences, Universidad de la Republica, Montevideo, Uruguay. jsotelosilveira@iibce.edu.uy.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Sotelo-Silveira
mesh_terms: D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental; D008018:Life Cycle Stages; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods*; D015800:Protozoan Proteins / Q000032:analysis; D016053:RNA, Protozoan / Q000032:analysis; D012270:Ribosomes / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015800:Protozoan Proteins; D016053:RNA, Protozoan