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Comparative proteomics of the two T. brucei PABPs suggests that PABP2 controls bulk mRNA
- Source :
- PLoS Neglected Tropical Diseases, Vol 12, Iss 7, p e0006679 (2018), PLoS Neglected Tropical Diseases
- Publication Year :
- 2018
- Publisher :
- Public Library of Science (PLoS), 2018.
-
Abstract
- Poly(A)-binding proteins (PABPs) regulate mRNA fate by controlling stability and translation through interactions with both the poly(A) tail and eIF4F complex. Many organisms have several paralogs of PABPs and eIF4F complex components and it is likely that different eIF4F/PABP complex combinations regulate distinct sets of mRNAs. Trypanosomes have five eIF4G paralogs, six of eIF4E and two PABPs, PABP1 and PABP2. Under starvation, polysomes dissociate and the majority of mRNAs, most translation initiation factors and PABP2 reversibly localise to starvation stress granules. To understand this more broadly we identified a protein interaction cohort for both T. brucei PABPs by cryo-mill/affinity purification-mass spectrometry. PABP1 very specifically interacts with the previously identified interactors eIF4E4 and eIF4G3 and few others. In contrast PABP2 is promiscuous, with a larger set of interactors including most translation initiation factors and most prominently eIF4G1, with its two partners TbG1-IP and TbG1-IP2. Only RBP23 was specific to PABP1, whilst 14 RNA-binding proteins were exclusively immunoprecipitated with PABP2. Significantly, PABP1 and associated proteins are largely excluded from starvation stress granules, but PABP2 and most interactors translocate to granules on starvation. We suggest that PABP1 regulates a small subpopulation of mainly small-sized mRNAs, as it interacts with a small and distinct set of proteins unable to enter the dominant pathway into starvation stress granules and localises preferentially to a subfraction of small polysomes. By contrast PABP2 likely regulates bulk mRNA translation, as it interacts with a wide range of proteins, enters stress granules and distributes over the full range of polysomes.<br />Author summary Poly(A)-binding proteins (PABPs) bind to the poly(A) tails of eukaryotic mRNAs and function in regulating mRNA fate. Many eukaryotes have several PABP paralogs and the current view is that each PABP binds a specific subset of mRNAs. Trypanosoma brucei has two PABPs, and to understand the differential functionality of these paralogs we identified interacting proteins for each. We found unique interactors for both PABPs, and significant differences between the two interaction cohorts. Our data indicate that the two PABP paralogs of trypanosomes have very distinct roles in mediating mRNA fate.
- Subjects :
- Proteomics
Trypanosoma
Cell Physiology
lcsh:Arctic medicine. Tropical medicine
lcsh:RC955-962
Trypanosoma brucei brucei
Protozoan Proteins
Gene Expression
Fractional Precipitation
RNA-binding proteins
Research and Analysis Methods
Poly(A)-Binding Protein I
Poly(A)-Binding Protein II
Biochemistry
Cell Fusion
Genetics
Trypanosoma Brucei
ddc:610
RNA, Messenger
Protozoans
Translation Initiation
Salting Out
Messenger RNA
lcsh:Public aspects of medicine
Organisms
Biology and Life Sciences
Eukaryota
Proteins
lcsh:RA1-1270
Cell Biology
Parasitic Protozoans
Precipitation Techniques
Nucleic acids
Eukaryotic Initiation Factor-4E
RNA
Protein Translation
Protein Binding
Research Article
Trypanosoma Brucei Gambiense
Subjects
Details
- Language :
- English
- ISSN :
- 19352735 and 19352727
- Volume :
- 12
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS Neglected Tropical Diseases
- Accession number :
- edsair.pmid.dedup....e5321df5dbe31c790e8ba6e634028756