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


Type
Article
Change log
Authors
Chow, Eugene Yui-Ching  ORCID logo  https://orcid.org/0000-0002-5575-6724
Harris, Lynne M 
Liew, Shiau Wei 
Jensen, Anders 
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.

Description

Funder: Hong Kong PhD Fellowship Scheme


Funder: Hong Kong Special Administrative Region Government

Keywords
Base Sequence, G-Quadruplexes, Gene Expression Profiling, Gene Expression Regulation, Gene Ontology, Humans, Malaria, Falciparum, Mutation, Nucleotide Motifs, Plasmodium falciparum, Protein Biosynthesis, Protozoan Proteins, RNA, Messenger, RNA, Protozoan, RNA-Seq, Ribosomes
Journal Title
Nucleic Acids Res
Conference Name
Journal ISSN
0305-1048
1362-4962
Volume Title
49
Publisher
Oxford University Press (OUP)
Sponsorship
Medical Research Council (MR/P010873/2)
Isaac Newton Trust (19.07(h))
Medical Research Council (MR/R021821/1)
UK Medical Research Council [grants MR/K000535/1 and MR/L008823/1] to CJM. Shenzhen Basic Research Project [JCYJ20180507181642811], Research Grants Council of the Hong Kong SAR, China Projects [CityU 11100421, CityU 11101519, CityU 11100218, N_CityU110/17, CityU 21302317], Croucher Foundation [Project No. 9500030, 9509003], State Key Laboratory of Marine Pollution Director Discretionary Fund, City University of Hong Kong [projects 6000711, 7005503, 9667222, 9680261] to CKK. A generous donation from Mr. and Mrs. Sunny Yang, the University Grants Committee Area of Excellence Scheme (AoE/M-403/16), and the Innovation and Technology Commission, Hong Kong Special Administrative Region Government to the State Key Laboratory of Agrobiotechnology (CUHK) to TFC. EYCC was supported by the Hong Kong PhD Fellowship Scheme.