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dc.contributor.authorDumetz, Franck
dc.contributor.authorChow, Eugene Yui-Ching
dc.contributor.authorHarris, Lynne M
dc.contributor.authorLiew, Shiau Wei
dc.contributor.authorJensen, Anders
dc.contributor.authorUmar, Mubarak I
dc.contributor.authorChung, Betty
dc.contributor.authorChan, Ting Fung
dc.contributor.authorMerrick, Catherine
dc.contributor.authorKwok, Chun Kit
dc.date.accessioned2022-01-07T16:50:46Z
dc.date.available2022-01-07T16:50:46Z
dc.date.issued2021-12-02
dc.identifier.issn0305-1048
dc.identifier.otherPMC8643661
dc.identifier.other34792144
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332386
dc.descriptionFunder: Hong Kong PhD Fellowship Scheme
dc.descriptionFunder: Hong Kong Special Administrative Region Government
dc.description.abstractG-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.
dc.description.sponsorshipUK 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.
dc.languageeng
dc.publisherOxford University Press (OUP)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1362-4962
dc.sourcenlmid: 0411011
dc.titleG-quadruplex RNA motifs influence gene expression in the malaria parasite Plasmodium falciparum.
dc.typeArticle
dc.date.updated2022-01-07T16:50:46Z
prism.endingPage12501
prism.issueIdentifier21
prism.publicationNameNucleic Acids Res
prism.startingPage12486
prism.volume49
dc.identifier.doi10.17863/CAM.79832
dcterms.dateAccepted2021-10-21
rioxxterms.versionofrecord10.1093/nar/gkab1095
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidDumetz, Franck [0000-0001-8790-9986]
dc.contributor.orcidChow, Eugene Yui-Ching [0000-0002-5575-6724]
dc.contributor.orcidChung, Betty [0000-0003-4384-285X]
dc.contributor.orcidChan, Ting Fung [0000-0002-0489-3884]
dc.contributor.orcidMerrick, Catherine [0000-0001-7583-2176]
dc.identifier.eissn1362-4962
pubs.funder-project-idMedical Research Council (MR/P010873/2)
pubs.funder-project-idIsaac Newton Trust (19.07(h))
pubs.funder-project-idMedical Research Council (MR/R021821/1)
cam.issuedOnline2021-11-18


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International