Targeting and function of proteins mediating translation initiation in organelles of Plasmodium falciparum. Issue 4 (16th March 2015)

• Record Type: Journal Article
• Authors: Haider, Afreen; Allen, Stacey M.; Jackson, Katherine E.; Ralph, Stuart A.; Habib, Saman
• Is Part Of: Molecular microbiology. Volume 96:Issue 4(2015)
• Page Start: 796
• Page End: 814
• Publication Date: 2015-03-16
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12972
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>The malaria parasite <italic>P</italic><italic>lasmodium falciparum</italic> has two translationally active organelles – the apicoplast and mitochondrion, which import nuclear‐encoded translation factors to mediate protein synthesis. Initiation of translation is a complex step wherein initiation factors (IFs) act in a regulated manner to form an initiation complex. We identified putative organellar IFs and investigated the targeting, structure and function of IF1, IF2 and IF3 homologues encoded by the parasite nuclear genome. A single <italic>Pf</italic>IF1 is targeted to the apicoplast. Apart from its critical ribosomal interactions, <italic>Pf</italic>IF1 also exhibited nucleic‐acid binding and melting activities and mediated transcription anti‐termination. This suggests a prominent ancillary function for <italic>Pf</italic>IF1 in destabilisation of DNA and RNA hairpin loops encountered during transcription and translation of the A+T rich apicoplast genome. Of the three putative IF2 homologues, only one (<italic>Pf</italic>IF2a) was an organellar protein with mitochondrial localisation. We additionally identified an IF3 (<italic>Pf</italic>IF3a) that localised exclusively to the mitochondrion and another protein, <italic>Pf</italic>IF3b, that was apicoplast targeted. <italic>Pf</italic>IF3a exhibited ribosome anti‐association activity, and monosome splitting by <italic>Pf</italic>IF3a was enhanced by ribosome recycling factor (<italic>Pf</italic>RRF2) and <italic>Pf</italic>EF‐G<sub>M</sub><sub>it</sub>. These results fill a gap in our understanding of organellar translation in <italic>P</italic><italic>lasmodium</italic>, which is the site of action of several anti‐malarial compounds.</p> </abstract>