A divergent nonsense-mediated decay machinery in Plasmodium falciparum is inefficient and non-essential release_6lz2oj67vrh7texsmozjk5cwdy

Abstract

Nonsense-mediated decay (NMD) is a conserved mRNA quality control process that eliminates transcripts bearing a premature termination codon. In addition to its role in removing erroneous transcripts, NMD is involved in post-transcriptional regulation of gene expression via programmed intron retention in metazoans. The apicomplexan parasite <jats:italic>Plasmodium falciparum</jats:italic> shows relatively high levels of intron retention, but it is unclear whether these variant transcripts are functional targets of NMD. In this study, we use CRISPR-Cas9 to disrupt and epitope-tag two core NMD components: <jats:italic>Pf</jats:italic>UPF1 (PF3D7_1005500) and <jats:italic>Pf</jats:italic>UPF2 (PF3D7_0925800). Using RNA-seq, we find that NMD in <jats:italic>P. falciparum</jats:italic> is highly derived and requires UPF2, but not UPF1 for transcript degradation. Furthermore, our work suggests that the majority of intron retention in <jats:italic>P. falciparum</jats:italic> has no functional role and that NMD is not required for parasite growth ex vivo. We localise both <jats:italic>Pf</jats:italic>UPF1 and <jats:italic>Pf</jats:italic>UPF2 to puncta within the parasite cytoplasm, which may represent processing bodies - ribonucleoparticles that are sites of cytoplasmic mRNA decay. Finally, we identify a number of mRNA-binding proteins that co-immunoprecipitate with the NMD core complex and propose a model for a divergent NMD that does not require <jats:italic>Pf</jats:italic>UPF1 and incorporates novel accessory proteins to elicit mRNA decay.
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