G-quadruplex RNA motifs influence gene expression in the malaria parasite Plasmodium falciparum

Abstract G-quadruplexes are non-helical secondary structures that can fold in vivo in both DNA and RNA. In human cells, they can influence replication, transcription and telomere maintenance in DNA, or translation, transcript processing and stability of RNA. We have previously showed that G-quadrupl...

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Bibliographic Details
Published in:Nucleic acids research 2021-12, Vol.49 (21), p.12486-12501
Main Authors: Dumetz, Franck, Chow, Eugene Yui-Ching, Harris, Lynne M, Liew, Shiau Wei, Jensen, Anders, Umar, Mubarak I, Chung, Betty, Chan, Ting Fung, Merrick, Catherine J, Kwok, Chun Kit
Format: Article
Language:English
Subjects:
Base Sequence
G-Quadruplexes
Gene Expression Profiling - methods
Gene Expression Regulation
Gene Ontology
Humans
Malaria, Falciparum - parasitology
Mutation
Nucleotide Motifs - genetics
Plasmodium falciparum - genetics
Plasmodium falciparum - physiology
Protein Biosynthesis - genetics
Protozoan Proteins - genetics
Protozoan Proteins - metabolism
Ribosomes - genetics
Ribosomes - metabolism
RNA and RNA-protein complexes
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA, Protozoan - chemistry
RNA, Protozoan - genetics
RNA, Protozoan - metabolism
RNA-Seq - methods
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Summary:Abstract G-quadruplexes are non-helical secondary structures that can fold in vivo in both DNA and RNA. In human cells, they can influence replication, transcription and telomere maintenance in DNA, or translation, transcript processing and stability of RNA. We have previously showed that G-quadruplexes are detectable in the DNA of the malaria parasite Plasmodium falciparum, despite a very highly A/T-biased genome with unusually few guanine-rich sequences. Here, we show that RNA G-quadruplexes can also form in P. falciparum RNA, using rG4-seq for transcriptome-wide structure-specific RNA probing. Many of the motifs, detected here via the rG4seeker pipeline, have non-canonical forms and would not be predicted by standard in silico algorithms. However, in vitro biophysical assays verified formation of non-canonical motifs. The G-quadruplexes in the P. falciparum transcriptome are frequently clustered in certain genes and associated with regions encoding low-complexity peptide repeats. They are overrepresented in particular classes of genes, notably those that encode PfEMP1 virulence factors, stress response genes and DNA binding proteins. In vitro translation experiments and in vivo measures of translation efficiency showed that G-quadruplexes can influence the translation of P. falciparum mRNAs. Thus, the G-quadruplex is a novel player in post-transcriptional regulation of gene expression in this major human pathogen.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkab1095