Format

Send to

Choose Destination
BMC Genomics. 2016 Apr 26;17:306. doi: 10.1186/s12864-016-2624-3.

Integrative analysis of the Trypanosoma brucei gene expression cascade predicts differential regulation of mRNA processing and unusual control of ribosomal protein expression.

Author information

1
Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, D-69120, Heidelberg, Germany.
2
Department of Molecular Cell Physiology, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
3
Systems Bioinformatics, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
4
Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), 307 Westlake Ave N, Seattle, WA, 98109-5219, USA.
5
Current address: Biology of Host Parasite Interactions, 25 rue du Docteur Roux, 75724, Paris cedex 15, France.
6
Centre for Immunity, Infection and Evolution, Institute for Immunology and infection Research, School of Biological Sciences, Ashworth Laboratories, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JT, UK.
7
Department of Global Health, University of Washington, Harris Hydraulics Building, 1705 NE Pacific St #310E, Box 357965, Seattle, WA, 98195, USA.
8
Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, 98195, USA.
9
Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, D-69120, Heidelberg, Germany. cclayton@zmbh.uni-heidelberg.de.

Abstract

BACKGROUND:

Trypanosoma brucei is a unicellular parasite which multiplies in mammals (bloodstream form) and Tsetse flies (procyclic form). Trypanosome RNA polymerase II transcription is polycistronic, individual mRNAs being excised by trans splicing and polyadenylation. We previously made detailed measurements of mRNA half-lives in bloodstream and procyclic forms, and developed a mathematical model of gene expression for bloodstream forms. At the whole transcriptome level, many bloodstream-form mRNAs were less abundant than was predicted by the model.

RESULTS:

We refined the published mathematical model and extended it to the procyclic form. We used the model, together with known mRNA half-lives, to predict the abundances of individual mRNAs, assuming rapid, unregulated mRNA processing; then we compared the results with measured mRNA abundances. Remarkably, the abundances of most mRNAs in procyclic forms are predicted quite well by the model, being largely explained by variations in mRNA decay rates and length. In bloodstream forms substantially more mRNAs are less abundant than predicted. We list mRNAs that are likely to show particularly slow or inefficient processing, either in both forms or with developmental regulation. We also measured ribosome occupancies of all mRNAs in trypanosomes grown in the same conditions as were used to measure mRNA turnover. In procyclic forms there was a weak positive correlation between ribosome density and mRNA half-life, suggesting cross-talk between translation and mRNA decay; ribosome density was related to the proportion of the mRNA on polysomes, indicating control of translation initiation. Ribosomal protein mRNAs in procyclics appeared to be exceptionally rapidly processed but poorly translated.

CONCLUSIONS:

Levels of mRNAs in procyclic form trypanosomes are determined mainly by length and mRNA decay, with some control of precursor processing. In bloodstream forms variations in nuclear events play a larger role in transcriptome regulation, suggesting aquisition of new control mechanisms during adaptation to mammalian parasitism.

PMID:
27118143
PMCID:
PMC4845500
DOI:
10.1186/s12864-016-2624-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center