Arginine Methyltransferases as Regulators of RNA-Binding Protein Activities in Pathogenic Kinetoplastids

Author(s)

Campagnaro, Gustavo D. ^[1] ; Nay, Edward ^[2] ; Plevin, Michael J. ^[2] ; Cruz, Angela K. ^[1] ; Walrad, Pegine B. ^[2]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol, Ribeirao Preto - Brazil

^[2] Univ York, York Biomed Res Inst, Dept Biol, York, N Yorkshire - England

• Document type: Review article
• Source: FRONTIERS IN MOLECULAR BIOSCIENCES; v. 8, JUN 11 2021.
• Web of Science Citations: 0

Abstract

A large number of eukaryotic proteins are processed by single or combinatorial post-translational covalent modifications that may alter their activity, interactions and fate. The set of modifications of each protein may be considered a ``regulatory code{''}. Among the PTMs, arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), can affect how a protein interacts with other macromolecules such as nucleic acids or other proteins. In fact, many RNA-binding (RBPs) proteins are targets of PRMTs. The methylation status of RBPs may affect the expression of their bound RNAs and impact a diverse range of physiological and pathological cellular processes. Unlike most eukaryotes, Kinetoplastids have overwhelmingly intronless genes that are arranged within polycistronic units from which mature mRNAs are generated by trans-splicing. Gene expression in these organisms is thus highly dependent on post-transcriptional control, and therefore on the action of RBPs. These genetic features make trypanosomatids excellent models for the study of post-transcriptional regulation of gene expression. The roles of PRMTs in controlling the activity of RBPs in pathogenic kinetoplastids have now been studied for close to 2 decades with important advances achieved in recent years. These include the finding that about 10% of the Trypanosoma brucei proteome carries arginine methylation and that arginine methylation controls Leishmania:host interaction. Herein, we review how trypanosomatid PRMTs regulate the activity of RBPs, including by modulating interactions with RNA and/or protein complex formation, and discuss how this impacts cellular and biological processes. We further highlight unique structural features of trypanosomatid PRMTs and how it contributes to their singular functionality. (AU)

• FAPESP's process: 18/14398-0 - UK:Brazil Joint Centre Partnership in Leishmaniasis (JCPiL)
• Grantee: Angela Kaysel Cruz
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/02372-6 - Actions coordinated by the enzyme Arginine Methyltransferase 5 of Leishmania braziliensis
• Grantee: Gustavo Daniel Campagnaro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/13618-8 - Regulating the trans-regulators: investigating the PRMT7 molecular pathway as an epigenetic regulator of Leishmania virulence
• Grantee: Angela Kaysel Cruz
• Support Opportunities: Research Projects - Thematic Grants