Post transcriptional control of gene expression in Leishmania

Abstract

Leishmania parasites are ancient eukaryotes, characterized by unusual molecular mechanisms. We have used the gene encoding for Hsp83 as a model system for studying regulatory mechanisms that control developmental gene regulation. We previously showed that protein coding genes are regulated exclusively by post-transcriptional mechanisms, while no transcriptional activation could be observed even for the conserved Hsp83 gene. We now show that processing and maturation of the Hsp83 polycistronic primary transcripts is more efficient at elevated temperatures. The mature transcripts are more stable during heat shock, with regulation conferred by 3' UTRs. Poly(A) tails of Hsp83 are approximately 30 nucleotides long, as common for other low eukaryotes. The mechanism that signals differential degradation is still unclear, since it was not possible to detect differences in deadenylation of Hsp83 transcripts at varying temperatures. Heat shock transcripts are preferentially translated at 33-37 degrees C, but unlike Drosophila, translational regulation is controlled by a region within the 3' UTR. Using this traditionally conserved system emphasizes that regulatory mechanisms in Leishmania differ from those prevailing in other eukaryotes.

TheHsp90–Sti1 interaction is critical forLeishmania donovaniproliferation in both life cycle stages

“…However, such an approach is not feasible for Hsp90 or Hsp70 since both proteins are encoded by multiple, tandemly arranged, identical gene copies in Leishmania spp. (Lee et al ., ; Hubel and Clos, ; Shapira et al ., ). So far, no tandem arrays of genes have been successfully targeted for replacement in Leishmania spp.…”

Identification of the HSP70-II gene in Leishmania braziliensis HSP70 locus: genomic organization and UTRs characterization

“…Although, the size difference between these transcripts could not be explained by the sole difference in size of both 3' UTRs, it is likely that the differences are due to different length of the poly(A) tail [42,43]. Noticeably, it is considered that unstable mRNAs carry shorter poly (A) tails [44,45]. Northern blot assays showed that the steady-state levels of both transcripts are not affected by the temperature of incubation.…”

LACK, a RACK1 ortholog, facilitates cytochrome c oxidase subunit expression to promote Leishmania major fitness

“…During infection, Leishmania promastigotes mount a heat stress response to elevated temperatures encountered following inoculation from the sandfly into the mammalian host. Such stress responses typically result in a generalized decrease in protein synthesis (Hunter et al, 1984;Shapira et al, 1988;Zilberstein and Shapira, 1994), albeit with an induction of specific proteins, such as heat shock proteins (Shapira et al, 2001). Significantly, this heat stress alone represents the primary physiologic signal for amastigote development (Zilberstein and Shapira, 1994;Alcolea et al, 2010), suggesting a link between heat stress and translational control in amastigote differentiation.…”