Coordinate regulation of a family of promastigote-enriched mRNAs by the 3′UTR PRE element in Leishmania mexicana

Post-transcriptional regulation is a key feature controlling gene expression in the protozoan parasite Leishmania. The nine-nucleotide paraflagellar rod regulatory element (PRE) in the 3′UTR of Leishmania mexicana PFR2 is both necessary and sufficient for the observed 10-fold higher level of PFR2 mRNA in promastigotes compared to amastigotes. It is also found in the 3′UTRs of all known PFR genes. A search of the Leishmania major Friedlin genomic database revealed several genes that share this cis element including a homolog of a heterotrimeric kinesin II subunit, and a gene that shares identity to a homolog of a Plasmodium antigen. In this study, we show that genes that harbor the PRE display promastigote-enriched transcript accumulation ranging from 4- to 15-fold. Northern analysis on episomal block substitution constructs revealed that the regulatory element is necessary for the proper steady-state accumulation of mRNA in L. mexicana paraflagellar rod gene 4 (PFR4). Also we show that the PRE plays a major role in the proper steady-state mRNA accumulation of PFR1, but may not account for the full regulatory mechanism acting on this mRNA. Our evidence suggests that the PRE coordinately regulates the mRNA abundance of not only the PFR family of genes, but also in a larger group of genes that have unrelated functions. Although the PRE alone can regulate some mRNAs, it may also act in concert with additional elements to control other RNA transcripts.