Research Article: Conserved motifs in nuclear genes encoding predicted mitochondrial proteins in Trypanosoma cruzi

Date Published: April 9, 2019

Publisher: Public Library of Science

Author(s): Lorena Becco, Pablo Smircich, Beatriz Garat, M Carolina Elias.


Trypanosoma cruzi, the protozoan parasite that causes Chagas’ disease, exhibits peculiar biological features. Among them, the presence of a unique mitochondrion is remarkable. Even though the mitochondrial DNA constitutes up to 25% of total cellular DNA, the structure and functionality of the mitochondrion are dependent on the expression of the nuclear genome. As in other eukaryotes, specific peptide signals have been proposed to drive the mitochondrial localization of a subset of trypanosomatid proteins. However, there are mitochondrial proteins encoded in the nuclear genome that lack of a peptide signal. In other eukaryotes, alternative protein targeting to subcellular organelles via mRNA localization has also been recognized and specific mRNA localization towards the mitochondria has been described. With the aim of seeking for mitochondrial localization signals in T. cruzi, we developed a strategy to build a comprehensive database of nuclear genes encoding predicted mitochondrial proteins (MiNT) in the TriTryps (T. cruzi, T. brucei and L. major). We found that approximately 15% of their nuclear genome encodes mitochondrial products. In T. cruzi the MiNT database reaches 1438 genes and a conserved peptide signal, M(L/F) R (R/S) SS, named TryM-TaPe is found in 60% of these genes, suggesting that the canonical mRNA guidance mechanism is present. In addition, the search for compositional signals in the transcripts of T. cruzi MiNT genes produce a list, being worth to note a conserved non-translated element represented by the consensus sequence DARRVSG. Taking into account its reported interaction with the T. brucei TRRM3 protein which is enriched in the mitochondrial membrane fraction, we here suggest a putative zip code role for this element. Globally, here we provide an inventory of the mitochondrial proteins in T. cruzi and give evidence for the existence of both peptide and mRNA signals specific to nuclear encoded mitochondrial proteins.

Partial Text

Trypanosoma cruzi (Kinetoplastidae, Trypanosomatidae) is the protozoan parasite that causes Chagas’ disease, also known as American trypanosomiasis [1]. This disease affects 6 to 7 millions of people, mostly from poor rural regions of 21 countries of Central and South America, where the vector responsible for the transmission to humans, diverse species of the Reduvidae, is found [2]. Nevertheless, since the parasite can also be transmitted by contaminated food, congenitally from mother to child and through contaminated blood or organ donations, disease has spread out world-wide.

Aiming to identify conserved signals among the nuclear genes encoding mitochondrial proteins in T. cruzi, we searched for the genes annotated as such in the TriTrypDB. Despite its availability since 2005 [50], and the many efforts to its improvement, completion and annotation from there on, we only obtained meager results. Thus, we undertook the task of obtaining a comprehensive list of nuclear genes encoding mitochondrial proteins which would not only serve as the dataset target for the aim of this work but also constitute by itself a contribution to the current state of the knowledge of T. cruzi genome. Following an in-silico strategy, a wide inventory of the nuclear genes encoding mitochondrial proteins, MiNT, in the TriTryps was obtained (1438, 1501 and 1558 for T. cruzi, T. brucei and L. major respectively). The search for enriched motifs in T. cruzi MiNT allowed the identification of a list of conserved signals. Signals involved in different metabolic steps were identified. For the well-known mitochondrial localization peptides, we could establish a consensus motifhere named TryM-TaPe, M(L/F) R (R/S) SS, present in 60% of T. cruzi MiNT database. In addition, a putative mitochondrial localization role is here proposed for the nucleic element DARRVSG that may be recognized by the conserved TRRM3 protein which is enriched in the mitochondrial membrane fraction in T. brucei. While work is in progress to analyze the role of this element, its actual interaction with TRRM3 and the function of this RBP, these findings suggest that in addition to the canonical peptide localization signal, mRNA localization could be guided to the mitochondria surroundings via zip code nucleic signals present in the UTRs in T. cruzi.