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

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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.
Original languageEnglish
Number of pages26
JournalWellcome Open Research
Volume5
Early online date21 Sep 2020
DOIs
Publication statusPublished - 18 Nov 2020

Keywords

  • low-complexity regions (LCRs)
  • proteome
  • phosphorylation
  • liquid-liquid phase separation
  • nucleic acid binding proteins
  • granules

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