An in silico study predicts the presence of conserved guanine quadruplex (G4) secondary structures in the DNA of Trypanosoma cruzi

SAYÉ, MELISA; MACIEL, BELEN; MIRANDA, MARIANA R.; REIGADA, CHANTAL; RENGIFO, MARCOS; GALCERAN, FACUNDO; PEREIRA, CLAUDIO A.

Evento virtual

Congreso; British Society for Parasitology Congress (Parasites on-line); 2021

British Society for Parasitology

Non-canonical forms of DNA like guanine quadruplex (G4) elements play important roles in regulating transcription and translation through interactions with their protein partners. Nucleoside Diphosphate Kinases (NDPKs) are multifunctional enzymes, some of them have been identified as G4-binding proteins, such as human NM23-H2 and maize ZmNDPK1, settling down an evolutionary conservation of this NDPKs feature. TcNDPK1 is the Trypanosoma cruzi homolog of NM23-H2 and ZmNDPK1 and different studies from our group associate TcNDPK1 with nuclear functions, for instance, in vitro nuclease and DNA-binding properties and, more recently, participation in DNA damage response machinery probably through the regulation of DNA repair enzymes expression. Very little is known about G4 elements in trypanosomes. In this work, considering that they might function as regulatory elements or as binding sites for NDPKs enzymes, an in silico search to identify putative G4 elements in the genome of T. cruzi was initiated. Homologous chromosomes Dm28c_6, Chr30P and TCC_10 from DM28c, CL Brener and TCC strains respectively, were analysed using the online available algorithms G4hunter and QGRS Mapper. 49, 41 and 47cannonical G4 elements were identified by both programmes for each chromosome respectively, which were distributed heterogeneously all along the chromosomes. Interestingly, more than 90 % of the G4 elements localize in the coding strand, about 65% are intergenic and 48% are in UTR regions. In addition, 80% are conserved among the three chromosomes. These results predict that G4 elements are present in the genome of T. cruzi and suggest that they may act as regulatory elements for gene expression where different proteins, e.g. TcNDPK1, could bind and exert its functions. Further investigations are needed to confirm these predictions.