eprintid: 20593 rev_number: 13 eprint_status: archive userid: 1589 dir: disk0/00/02/05/93 datestamp: 2016-04-26 08:35:34 lastmod: 2024-04-09 23:45:05 status_changed: 2016-04-26 08:35:34 type: article metadata_visibility: show creators_name: Antwi, Enoch B. creators_name: Haanstra, Jurgen R. creators_name: Ramasamy, Gowthaman creators_name: Jensen, Bryan creators_name: Droll, Dorothea creators_name: Rojas, Federico creators_name: Minia, Igor creators_name: Terrao, Monica creators_name: Mercé, Clémentine creators_name: Matthews, Keith creators_name: Myler, Peter J. creators_name: Parsons, Marilyn creators_name: Clayton, Christine title: Integrative analysis of the Trypanosoma brucei gene expression cascade predicts differential regulation of mRNA processing and unusual control of ribosomal protein expression subjects: ddc-570 divisions: i-706000 divisions: i-718000 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. date: 2016 publisher: BioMed Central; Springer id_scheme: DOI ppn_swb: 1656505568 own_urn: urn:nbn:de:bsz:16-heidok-205939 language: eng bibsort: ANTWIENOCHINTEGRATIV2016 full_text_status: public publication: BMC Genomics volume: 17 number: 306 place_of_pub: London; Berlin; Heidelberg pagerange: 1-16 issn: 1471-2164 citation: Antwi, Enoch B. ; Haanstra, Jurgen R. ; Ramasamy, Gowthaman ; Jensen, Bryan ; Droll, Dorothea ; Rojas, Federico ; Minia, Igor ; Terrao, Monica ; Mercé, Clémentine ; Matthews, Keith ; Myler, Peter J. ; Parsons, Marilyn ; Clayton, Christine (2016) Integrative analysis of the Trypanosoma brucei gene expression cascade predicts differential regulation of mRNA processing and unusual control of ribosomal protein expression. BMC Genomics, 17 (306). pp. 1-16. ISSN 1471-2164 document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/20593/1/12864_2016_Article_2624.pdf