Life cycle adapted upstream open reading frames (uORFs) inTrypanosoma congolense: A post-transcriptional approach to accurate gene regulation

Philipp Fervers , Florian Fervers , Wojciech Makałowski , Marcin Jąkalski


The presented work explores the regulatory influence of upstream open reading frames (uORFs) on gene expression in Trypanosoma congolense. More than 31,000 uORFs in total were identified and characterized here. We found evidence for the uORFs' appearance in the transcriptome to be correlated with proteomic expression data, clearly indicating their repressive potential in T. congolense, which has to rely on post-transcriptional gene expression regulation due to its unique genomic organization. Our data show that uORF's translation repressive potential does not only correlate with elemental sequence features such as length, position and quantity, but involves more subtle components, in particular the codon and amino acid profiles. This corresponds with the popular mechanistic model of a ribosome shedding initiation factors during the translation of a uORF, which can prevent reinitiation at the downstream start codon of the actual protein-coding sequence, due to the former extensive consumption of crucial translation components. We suggest that uORFs with uncommon codon and amino acid usage can slow down the translation elongation process in T. congolense, systematically deplete the limited factors, and restrict downstream reinitiation, setting up a bottleneck for subsequent translation of the protein-coding sequence. Additionally we conclude that uORFs dynamically influence the T. congolense life cycle. We found evidence that transition to epimastigote form could be supported by gain of uORFs due to alternative trans-splicing, which down-regulate housekeeping genes' expression and render the trypanosome in a metabolically reduced state of endurance.
Author Philipp Fervers
Philipp Fervers,,
, Florian Fervers
Florian Fervers,,
, Wojciech Makałowski
Wojciech Makałowski,,
, Marcin Jąkalski (FB / DPTNC)
Marcin Jąkalski,,
- Department of Plant Taxonomy and Nature Conservation
Journal seriesPLoS ONE, ISSN 1932-6203, (A 40 pkt)
Issue year2018
Publication size in sheets1.3
Article numbere0201461
ASJC Classification2700 General Medicine; 1100 General Agricultural and Biological Sciences; 1300 General Biochemistry, Genetics and Molecular Biology
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)40
Score sourcejournalList
ScoreMinisterial score = 40.0, 07-02-2020, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2017 = 1.111; WoS Impact Factor: 2018 = 2.776 (2) - 2018=3.337 (5)
Citation count*3 (2020-05-20)
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