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

Autor(es)

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

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo de Revisão
• Fonte: FRONTIERS IN MOLECULAR BIOSCIENCES; v. 8, JUN 11 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 18/14398-0 - Centro Reino-Unido-Brasil para o Estudo da Leishmaniose (JCPiL)
• Beneficiário: Angela Kaysel Cruz
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 20/02372-6 - Ações coordenadas pela enzima Arginina Metiltransferase 5 de Leishmania braziliensis
• Beneficiário: Gustavo Daniel Campagnaro
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/13618-8 - Regulando trans-reguladores: investigação da via molecular de PRMT7 como regulador epigenético da virulência em Leishmania
• Beneficiário: Angela Kaysel Cruz
• Modalidade de apoio: Auxílio à Pesquisa - Temático