{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:49:57Z","timestamp":1792205397670,"version":"4.4.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>It is widely accepted that the structure of RNA plays important roles in a number of biological processes, such as polyadenylation, splicing, and catalytic functions. Dynamic changes in RNA structure are able to regulate the gene expression programme and can be used as a highly specific and subtle mechanism for governing cellular processes. However, the nature of most RNA secondary structures in <jats:italic>Plasmodium falciparum<\/jats:italic> has not been determined. To investigate the genome-wide RNA secondary structural features at single-nucleotide resolution in <jats:italic>P. falciparum<\/jats:italic>, we applied a novel high-throughput method utilizing the chemical modification of RNA structures to characterize these structures. Structural data from parasites are in close agreement with the known 18S ribosomal RNA secondary structures of <jats:italic>P. falciparum<\/jats:italic> and can help to predict the <jats:italic>in vivo<\/jats:italic> RNA secondary structure of a total of 3,396 transcripts in the ring-stage and trophozoite-stage developmental cycles. By parallel analysis of RNA structures <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> during the <jats:italic>Plasmodium<\/jats:italic> parasite ring-stage and trophozoite-stage intraerythrocytic developmental cycles, we identified some key regulatory features. Recent studies have established that the RNA structure is a ubiquitous and fundamental regulator of gene expression. Our study indicate that there is a critical connection between RNA secondary structure and mRNA abundance during the complex biological programme of <jats:italic>P. falciparum<\/jats:italic>. This work presents a useful framework and important results, which may facilitate further research investigating the interactions between RNA secondary structure and the complex biological programme in <jats:italic>P. falciparum<\/jats:italic>. The RNA secondary structure characterized in this study has potential applications and important implications regarding the identification of RNA structural elements, which are important for parasite infection and elucidating host-parasite interactions and parasites in the environment.<\/jats:p>","DOI":"10.3389\/fcimb.2021.673966","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T16:54:41Z","timestamp":1621270481000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["In Vivo and In Vitro Genome-Wide Profiling of RNA Secondary Structures Reveals Key Regulatory Features in Plasmodium falciparum"],"prefix":"10.3389","volume":"11","author":[{"given":"Yanwei","family":"Qi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guixing","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingxia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1038\/s41587-020-0712-z","article-title":"Determination of Isoform-Specific RNA Structure With Nanopore Long Reads","volume":"39","author":"Aw","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"E3278","DOI":"10.1073\/pnas.1209823109","article-title":"Plasmodium falciparum Responds to Amino Acid Starvation by Entering Into a Hibernatory State","volume":"109","author":"Babbitt","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B3","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1146\/annurev-genet-120215-035034","article-title":"Genome-Wide Analysis of RNA Secondary Structure","volume":"50","author":"Bevilacqua","year":"2016","journal-title":"Annu. Rev. Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A Flexible Trimmer for Illumina Sequence Data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1471-2105-3-2","article-title":"The Comparative RNA Web (CRW) Site: An Online Database of Comparative Sequence and Structure Information for Ribosomal, Intron, and Other Rnas","volume":"3","author":"Cannone","year":"2002","journal-title":"BMC Bioinf."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20225748","article-title":"An Overview of Drug Resistance in Protozoal Diseases","volume":"20","author":"Capela","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1021\/bp970095h","article-title":"Controlling Messenger RNA Stability in Bacteria: Strategies for Engineering Gene Expression","volume":"13","author":"Carrier","year":"1997","journal-title":"Biotechnol. Prog."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD012688.pub2","article-title":"Indoor Residual Spraying for Preventing Malaria in Communities Using Insecticide-Treated Nets","volume":"5","author":"Choi","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e1005613","DOI":"10.1371\/journal.pgen.1005613","article-title":"Secondary Structure Across the Bacterial Transcriptome Reveals Versatile Roles in mRNA Regulation and Function","volume":"11","author":"Del Campo","year":"2015","journal-title":"PLoS Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1038\/nprot.2015.064","article-title":"Genome-Wide Profiling of In Vivo RNA Structure At Single-Nucleotide Resolution Using Structure-Seq","volume":"10","author":"Ding","year":"2015","journal-title":"Nat. Protoc."},{"key":"B11","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1038\/nature12756","article-title":"In Vivo Genome-Wide Profiling of RNA Secondary Structure Reveals Novel Regulatory Features","volume":"505","author":"Ding","year":"2014","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/418742a","article-title":"Thermoregulation in a Parasite\u2019s Life Cycle","volume":"418","author":"Fang","year":"2002","journal-title":"Nature"},{"key":"B13","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1074\/jbc.M308284200","article-title":"The Effects of Glucose Concentration on the Reciprocal Regulation of rRNA Promoters in Plasmodium falciparum","volume":"279","author":"Fang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/nprot.2016.011","article-title":"Transcriptome-Wide Interrogation of RNA Secondary Structure in Living Cells With Icshape","volume":"11","author":"Flynn","year":"2016","journal-title":"Nat. Protoc."},{"key":"B15","doi-asserted-by":"publisher","first-page":"121","DOI":"10.4161\/rna.23312","article-title":"DEAD Box RNA Helicase Functions in Cancer","volume":"10","author":"Fuller-Pace","year":"2013","journal-title":"RNA Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1038\/s41580-019-0136-0","article-title":"The Roles of Structural Dynamics in the Cellular Functions of Rnas","volume":"20","author":"Ganser","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1126\/science.3672135","article-title":"Structurally Distinct, Stage-Specific Ribosomes Occur in Plasmodium","volume":"238","author":"Gunderson","year":"1987","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1186\/s13059-014-0491-2","article-title":"Genome-Wide Profiling of Mouse RNA Secondary Structures Reveals Key Features of the Mammalian Transcriptome","volume":"15","author":"Incarnato","year":"2014","journal-title":"Genome Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"450","DOI":"10.4161\/rna.8.3.15388","article-title":"New Insights Into RNA Secondary Structure in the Alternative Splicing of Pre-Mrnas","volume":"8","author":"Jin","year":"2011","journal-title":"RNA Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s12864-018-4497-0","article-title":"RNA Secondary Structure Profiling in Zebrafish Reveals Unique Regulatory Features","volume":"19","author":"Kaushik","year":"2018","journal-title":"BMC Genomics"},{"key":"B21","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/nature09322","article-title":"Genome-Wide Measurement of RNA Secondary Structure in Yeast","volume":"467","author":"Kertesz","year":"2010","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.tibs.2015.02.005","article-title":"The RNA Structurome: Transcriptome-Wide Structure Probing With Next-Generation Sequencing","volume":"40","author":"Kwok","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"B23","doi-asserted-by":"crossref","first-page":"418","DOI":"10.2307\/3280287","article-title":"Synchronization of Plasmodium falciparum Erythrocytic Stages in Culture","volume":"65","author":"Lambros","year":"1979","journal-title":"J. Parasitol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"R25","DOI":"10.1186\/gb-2009-10-3-r25","article-title":"Ultrafast and Memory-Efficient Alignment of Short DNA Sequences to the Human Genome","volume":"10","author":"Langmead","year":"2009","journal-title":"Genome Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1261\/rna.058784.116","article-title":"Comparison of SHAPE Reagents for Mapping RNA Structures Inside Living Cells","volume":"23","author":"Lee","year":"2017","journal-title":"RNA"},{"key":"B26","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.celrep.2011.10.002","article-title":"Global Analysis of RNA Secondary Structure in Two Metazoans","volume":"1","author":"Li","year":"2012","journal-title":"Cell Rep."},{"key":"B27","doi-asserted-by":"publisher","first-page":"4346","DOI":"10.1105\/tpc.112.104232","article-title":"Regulatory Impact of RNA Secondary Structure Across the Arabidopsis Transcriptome","volume":"24","author":"Li","year":"2012","journal-title":"Plant Cell"},{"key":"B28","doi-asserted-by":"publisher","first-page":"11063","DOI":"10.1073\/pnas.1106501108","article-title":"Multiplexed RNA Structure Characterization With Selective 2 \u2018-Hydroxyl Acylation Analyzed by Primer Extension Sequencing (SHAPE-Seq)","volume":"108","author":"Lucks","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B29","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nature23009","article-title":"Nutrient Sensing Modulates Malaria Parasite Virulence","volume":"547","author":"Mancio-Silva","year":"2017","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","first-page":"4223","DOI":"10.1021\/ja043822v","article-title":"RNA Structure Analysis At Single Nucleotide Resolution by Selective 2\u2019-Hydroxyl Acylation and Primer Extension (SHAPE)","volume":"127","author":"Merino","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"B31","doi-asserted-by":"publisher","first-page":"REVIEWS0004","DOI":"10.1186\/gb-2002-3-3-reviews0004","article-title":"Untranslated Regions of Mrnas","volume":"3","author":"Mignone","year":"2002","journal-title":"Genome Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/nrg3681","article-title":"Insights Into RNA Structure and Function From Genome-Wide Studies","volume":"15","author":"Mortimer","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"B33","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.cell.2018.02.034","article-title":"Pervasive Regulatory Functions of mRNA Structure Revealed by High-Resolution Shape Probing","volume":"173","author":"Mustoe","year":"2018","journal-title":"Cell"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e00117","DOI":"10.1128\/mBio.00117-15","article-title":"Regulation of Plasmodium yoelii Oocyst Development by Strain- and Stage-Specific Small-Subunit Rrna","volume":"6","author":"Qi","year":"2015","journal-title":"MBio"},{"key":"B35","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"Bedtools: A Flexible Suite of Utilities for Comparing Genomic Features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"B36","doi-asserted-by":"publisher","first-page":"7237","DOI":"10.1073\/pnas.1523004113","article-title":"Temperature-Responsive In Vitro RNA Structurome of Yersinia Pseudotuberculosis","volume":"113","author":"Righetti","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B37","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/nature12894","article-title":"Genome-Wide Probing of RNA Structure Reveals Active Unfolding of mRNA Structures In Vivo","volume":"505","author":"Rouskin","year":"2014","journal-title":"Nature"},{"key":"B38","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/s0959-440x(02)00325-1","article-title":"RNA Folding In Vivo","volume":"12","author":"Schroeder","year":"2002","journal-title":"Curr. Opin. Struct. Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/nature14263","article-title":"Structural Imprints In Vivo Decode RNA Regulatory Mechanisms","volume":"519","author":"Spitale","year":"2015","journal-title":"Nature"},{"key":"B40","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/s41576-018-0034-x","article-title":"High-Throughput Determination of RNA Structures","volume":"19","author":"Strobel","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"B41","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/nature14280","article-title":"hiCLIP Reveals the In Vivo Atlas of mRNA Secondary Structures Recognized by Staufen 1","volume":"519","author":"Sugimoto","year":"2015","journal-title":"Nature"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1126\/science.aad8709","article-title":"From the RNA World to the Clinic","volume":"352","author":"Sullenger","year":"2016","journal-title":"Science"},{"key":"B43","doi-asserted-by":"publisher","first-page":"12170","DOI":"10.1073\/pnas.1807988115","article-title":"Genome-Wide RNA Structurome Reprogramming by Acute Heat Shock Globally Regulates mRNA Abundance","volume":"115","author":"Su","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B44","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1261\/rna.042218.113","article-title":"Mod-Seq: High-Throughput Sequencing for Chemical Probing of RNA Structure","volume":"20","author":"Talkish","year":"2014","journal-title":"RNA"},{"key":"B45","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1126\/science.781840","article-title":"Human Malaria Parasites in Continuous Culture","volume":"193","author":"Trager","year":"1976","journal-title":"Science"},{"key":"B46","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1146\/annurev-arplant-043015-111754","article-title":"The Conservation and Function of RNA Secondary Structure in Plants","volume":"67","author":"Vandivier","year":"2016","journal-title":"Annu. Rev. Plant Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1261\/rna.1166808","article-title":"Shapefinder: A Software System for High-Throughput Quantitative Analysis of Nucleic Acid Reactivity Information Resolved by Capillary Electrophoresis","volume":"14","author":"Vasa","year":"2008","journal-title":"Rna-a Publ. RNA Soc."},{"key":"B48","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/nrg3049","article-title":"Understanding the Transcriptome Through RNA Structure","volume":"12","author":"Wan","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"B49","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1038\/nature12946","article-title":"Landscape and Variation of RNA Secondary Structure Across the Human Transcriptome","volume":"505","author":"Wan","year":"2014","journal-title":"Nature"},{"key":"B50","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/978-1-62703-667-2_9","article-title":"Chemical Probing of RNA in Living Cells","volume":"1086","author":"Wildauer","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"e03080","DOI":"10.7554\/eLife.03080","article-title":"Cryo-EM Structure of the Plasmodium falciparum 80S Ribosome Bound to the Anti-Protozoan Drug Emetine","volume":"3","author":"Wong","year":"2014","journal-title":"Elife"},{"key":"B52","volume-title":"World Malaria Report 2020","year":"2020"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001141","article-title":"Genome-Wide Double-Stranded Rna Sequencing Reveals the Functional Significance of Base-Paired RNAs in Arabidopsis","volume":"6","author":"Zheng","year":"2010","journal-title":"PLoS Genet."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.673966\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T16:54:46Z","timestamp":1621270486000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.673966\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,17]]},"references-count":53,"alternative-id":["10.3389\/fcimb.2021.673966"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.673966","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,17]]},"article-number":"673966"}}