Intron splicing is a precisely regulated process, where only four intron sequences guide spliceosome machinery. They are: the exon-intron junction at the 5′ and 3′ end of the introns (5′ss – GT, 3′ss – AG); the branch site sequence located upstream of the 3′ss; and the polypyrimidine tract located between

the 3′ss and the branch site [6]. The aquatic fungus Blastocladiella emersonii belongs to the Chytridiomycete class, which is at the base of the fungal phylogenetic tree [7, 8]. Throughout its life cycle this fungus suffers dramatic biochemical and morphological changes, especially during two distinct stages of cell differentiation: germination and sporulation [9]. Both stages can be induced with a high degree of synchrony, and drastic changes in the patterns of RNA and Citarinostat in vivo protein syntheses are observed throughout the fungus life cycle. In nature, B. emersonii can Fosbretabulin be exposed to distinct environmental conditions, as temperature fluctuations and presence of heavy metals, as cadmium, that could lead to the disruption of some cellular functions. It was previously shown that the splicing machinery is sensitive to thermal stress, as exposure of Saccharomyces cerevisiae cells to heat shock at 42°C leads to the accumulation

of pre-mRNA species containing unspliced introns [10]. This splicing inhibition was also observed in a variety of species from yeast to humans, including B. emersonii [10–14]. However, the splicing machinery seems to be more thermoresistant in B. emersonii because at the lethal temperature of 42°C, when cell viability falls to less than 1% and protein synthesis is decreased by more than 95% [15], splicing selleck inhibitor is only partially inhibited in this fungus (30% inhibition) [13]. In yeast and Drosophila melanogaster at extreme temperatures splicing is inhibited more than 70% [10, 11]. Although the effects of heat shock in the splicing machinery have been known for more

than two decades [11], there is little information in the literature about how cadmium affects this complex. Cadmium (Cd2+) is a divalent cation present in polluted environments, which causes oxidative stress, lipid peroxidation and mutagenesis in the cells [16, 17]. However, the molecular mechanisms by which cadmium leads to ABT-263 clinical trial reactive oxygen species production and oxidative stress are largely unknown and are probably indirect. The mechanism usually proposed for cadmium toxicity is its binding to cellular proteins, resulting in the inhibition of some essential enzymes. As cadmium has high affinity for thiol groups, it is thought to bind accessible cysteine residues in proteins [16]. Another possible effect of cadmium exposure is the displacement of zinc and calcium from metalloproteins, leading to inhibition of these important proteins [16–18]. In this way, the presence of cadmium in the cells could affect, in theory, any biological process including the spliceosome machinery.

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