Post transcriptional control of gene expression in Leishmania

Michal Shapira, Alon Zilka, Srinivas Garlapati, Edit Dahan, Irit Dahan, Victoria Yavesky

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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°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. The genomes of kinetoplastid organisms exhibit unique and unusual features. Genes transcribed by RNA polymerase II are transcribed from polycistronic transcription units, and polygene clusters encode several abundant proteins. No evidence was found for transcriptional activation of developmentally regulated genes and mRNA levels are determined exclusively by post-transcriptional mechanisms. These include differential processing of the polycistronic transcripts and alternating rates of mRNA decay [1, 2, 3]. Polycistronic transcripts mature by trans-splicing that adds a short capped leader (39mer) to the 5'-end of mRNAs, and by 3' processing that involves cleavage and polyadenylation. Although trans-splicing of primary transcripts precedes their polyadenylation, the two mechanisms are coupled in kinetoplastids [4]. Polyadenylation occurs ∼250 nucleotides (nts) upstream of the trans-splicing site [5] and regulatory signals that consist of polypyrimidine tracks and AG splice sites serve as signal for both mechanisms [6]. The consensus AATAAA element for polyadenylation was not found in any of the genes examined to date.

Original languageEnglish
Pages (from-to)23-26
Number of pages4
JournalMedical Microbiology and Immunology
Volume190
Issue number1-2
DOIs
StatePublished - 1 Jan 2001

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