In silico analysis and developmental expression of ubiquitin-conjugating enzymes in Schistosoma mansoni

Abstract

Ubiquitin-conjugating enzymes (Ub-E2) perform the second step of ubiquitination and, consequently, are essential for regulating proteolysis and for modulating protein function, interactions and trafficking. Previously, our group demonstrated the crucial role of ubiquitination and the Ub-proteasome pathway during the Schistosoma mansoni life cycle. In the present investigation, we used a homology-based genome-wide bioinformatics approach to identify and molecularly characterise the Ub-E2 enzymes in S. mansoni. The putative functions were further investigated through molecular phylogenetic and expression profile analyses using cercariae, adult worms, eggs and mechanically transformed schistosomula (MTS) cultured in vitro for 3.5 h or 1 or 3 days. We identified, via in silico analysis, 17 Ub-E2 enzymes with conserved structural characteristics: the beta-sheet and the helix-2 form a central core bordered by helix-1 at one side and helix-3 and helix-4 at the other. The observed quantitative differences in the steady-state transcript levels between the cercariae and adult worms may contribute to the differential protein ubiquitination observed during the parasite's life cycle. This study is the first to identify and characterise the E2 ubiquitin conjugation family in S. mansoni and provides fundamental information regarding their molecular phylogenetics and developmental expression during intra-mammalian stages.

Identification of 170 New Long Noncoding RNAs in Schistosoma mansoni

“…It is implicated in protein ubiquitination, proteolysis, and degradation and was set as essential to S. mansoni biology [ 49 ]. Moreover, the Sm-lncRNA 12 is differentially expressed in S. mansoni and occupies the neighborhood of E2 gene [ 50 ], leading us to hypothesize this participation on ubiquitin proteasome regulation. These findings reinforce themselves because differentially expressed lncRNAs, identified from human placentas, may regulate their associated mRNAs through several mechanisms and connect the UPS with infection-inflammation pathways [ 51 ].…”

Functional conservation of an ancestral Pellino protein in helminth species

“…In helminths, phosphorylation and ubiquitination play important roles in maintaining homeostasis and regulating complex cellular adaptations 25 26 . Helminths process extracellular signals from the environment via specialized sensory receptors, inducing biological change through non-linear intracellular signal transduction pathways 25 .…”

“…Phosphorylation, and indeed de-phosphorylation, of serine and threonine residues specifically regulates the activity status of effector and adaptor proteins to facilitate the integration of signalling networks. Furthermore, there are a number of ubiquitination-related proteins expressed in helminths, including ubiquitin-conjugating enzymes (Ub-E2), small-ubiquitin related modifier (SUMO), the SUMO-pathway homologues SmT3B and SmT3C, and a ring-box protein (SmRbx) 26 27 28 . These proteins are functionally homologous to mammalian proteins with differential expression profiles throughout the life cycle of helminths.…”