Epitranscriptome machinery in Trypanosomatids: new players on the table?

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Date
2021Author
Maran, Suellen Rodrigues [UNIFESP]
Pitta, João Luiz de Lemos Padilha
Vasconcelos, Crhisllane Rafaele dos Santos
McDermott, Suzanne M.
Rezende, Antonio Mauro
Moretti, Nilmar Silvio
Type
ArtigoIs part of
Molecular MicrobiologyDOI
10.1111/mmi.14688Metadata
Show full item recordAbstract
Trypanosoma and Leishmania parasites cause devastating tropical diseases resulting in serious global health consequences. These organisms have complex life cycles with mammalian hosts and insect vectors. The parasites must, therefore, survive in dif- ferent environments, demanding rapid physiological and metabolic changes. These responses depend upon regulation of gene expression, which primarily occurs post- transcriptionally. Altering the composition or conformation of RNA through nucleotide modifications is one posttranscriptional mechanism of regulating RNA fate and func- tion, and modifications including N6-methyladenosine (m6A), N1-methyladenosine (m1A), N5-methylcytidine (m5C), N4-acetylcytidine (ac4C), and pseudouridine (Ψ), dynamically regulate RNA stability and translation in diverse organisms. Little is known about RNA modifications and their machinery in Trypanosomatids, but we hypothesize that they regulate parasite gene expression and are vital for survival. Here, we identified Trypanosomatid homologs for writers of m1A, m5C, ac4C, and Ψ and analyze their evolutionary relationships. We systematically review the evidence for their functions and assess their potential use as therapeutic targets. This work provides new insights into the roles of these proteins in Trypanosomatid parasite bi- ology and treatment of the diseases they cause and illustrates that Trypanosomatids provide an excellent model system to study RNA modifications, their molecular, cel- lular, and biological consequences, and their regulation and interplay.
Keywords
ac4Cm1A
m5C
Pseudouridine
RNA modification
Sponsorship
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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- EPM - Artigos [16058]