A global analysis of low-complexity regions in the Trypanosoma brucei proteome reveals enrichment in the C-terminus of nucleic acid binding proteins providing potential targets of phosphorylation.

Mathieu Cayla,Keith R Matthews,Alasdair C Ivens

doi:10.12688/wellcomeopenres.16286.2

Abstract

Background: Low-complexity regions (LCRs) on proteins have attracted increasing attention recently due to their role in the assembly of membraneless organelles or granules by liquid-liquid phase separation. Several examples of such granules have been shown to sequester RNA and proteins in an inactive state, providing an important mechanism for dynamic post-transcriptional gene regulation. In trypanosome parasites, post-transcriptional control overwhelmingly dominates gene regulation due to the organisation of their genome into polycistronic transcription units. The purpose of the current study was to generate a substantially more comprehensive genome-wide survey of LCRs on trypanosome proteins than currently available . Methods: Using the Shannon's entropy method, provided in the R package 'entropy', we identified LCRs in the proteome of Trypanosoma brucei. Our analysis predicts LCRs and their positional enrichment in distinct protein cohorts and superimposes on this a range of post-translational modifications derived from available experimental datasets. Results: We have identified 8162 LCRs present on 4914 proteins, representing 42% of the proteome, placing Trypanosoma brucei among the eukaryotes with the highest percentage of LCRs . Our results highlight the enrichment of LCRs in the C-terminal region of predicted nucleic acid binding proteins, these acting as favoured sites for potential phosphorylation. Phosphorylation represents 51% of the post-translational modifications present on LCRs compared to 16% on the rest of the proteome. Conclusions: The post-translational modifications of LCRs, and in particular phosphorylation events, could contribute to post-transcriptional gene expression control and the dynamics of protein targeting to membraneless organelles in kinetoplastid parasites.

Highlights

Introduction "By inference from what is known for other model eukaryotes, it is plausible that the aggregation into membraneless structures could be influenced by the presence and/or distribution of Low-complexity regions (LCRs) in the protein sequences themselves."
We confirmed the enrichment of phosphorylation events in LCRs, compared to other defined domains, even after normalisation by the frequency of representation of the amino acid on which it has been detected
Our analysis provides an enhanced description of LCRs across the trypanosome proteome and highlights their enrichment in the C-terminal region of predicted nucleic acid binding proteins

Summary

Introduction

Introduction "By inference from what is known for other model eukaryotes, it is plausible that the aggregation into membraneless structures could be influenced by the presence and/or distribution of LCRs in the protein sequences themselves.". Low-complexity regions (LCRs) on proteins have attracted increasing attention recently due to their role in the assembly of membraneless organelles or granules by liquid-liquid phase separation. Several examples of such granules have been shown to sequester RNA and proteins in an inactive state, providing an important mechanism for dynamic post-transcriptional gene regulation. Results: We have identified 8162 LCRs present on 4914 proteins, representing 42% of the proteome, placing Trypanosoma brucei among the eukaryotes with the highest percentage of LCRs. Our results highlight the enrichment of LCRs in the C-terminal region of predicted nucleic acid binding proteins, these acting as favoured sites for potential phosphorylation. Phosphorylation represents 51% of the post-translational modifications present on LCRs compared to 16% on the rest of the proteome

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Discussion

Conclusion