Deep Profiling of the Novel Intermediate-Size Noncoding RNAs in Intraerythrocytic Plasmodium falciparum

Wei, Chunyan; Xiao, Tengfei; Zhang, Peng; Wang, Zhensheng; Chen, Xiaowei; Zhang, Lian-Hui; Yao, Meixue; Chen, Runsheng; Wang, Heng

doi:10.1371/journal.pone.0092946

Cited by 13 publications

(11 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, in P. falciparum ncRNAs have been associated with regulation of virulence genes (31,32). Various ncRNA transcripts have been detected by different methods (33–37). Telomeres produce long ncRNAs that localize to a distinct nuclear compartment that does not overlap with telomere clusters (38,39).…”

Section: Introductionmentioning

confidence: 99%

Trans-acting GC-rich non-coding RNA atvarexpression site modulates gene counting in malaria parasite

2016

View full text Add to dashboard Cite

Monoallelic expression of the var multigene family enables immune evasion of the malaria parasite Plasmodium falciparum in its human host. At a given time only a single member of the 60-member var gene family is expressed at a discrete perinuclear region called the ‘var expression site’. However, the mechanism of var gene counting remains ill-defined. We hypothesize that activation factors associating specifically with the expression site play a key role in this process. Here, we investigate the role of a GC-rich non-coding RNA (ncRNA) gene family composed of 15 highly homologous members. GC-rich genes are positioned adjacent to var genes in chromosome-central gene clusters but are absent near subtelomeric var genes. Fluorescence in situ hybridization demonstrates that GC-rich ncRNA localizes to the perinuclear expression site of central and subtelomeric var genes in trans. Importantly, overexpression of distinct GC-rich ncRNA members disrupts the gene counting process at the single cell level and results in activation of a specific subset of var genes in distinct clones. We identify the first trans-acting factor targeted to the elusive perinuclear var expression site and open up new avenues to investigate ncRNA function in antigenic variation of malaria and other protozoan pathogens.

show abstract

Section: Introductionmentioning

confidence: 99%

Trans-acting GC-rich non-coding RNA atvarexpression site modulates gene counting in malaria parasite

2016

View full text Add to dashboard Cite

show abstract

“…Yet, little is known about its control beyond the epigenetic regulation of multigene families such as var , stevor , and rifin [ 7 , 8 ] and the specialized regulatory roles of some of the 27 putative ApiAP2 transcription factors [ 9 , 10 ]. Moreover, recent high throughput sequencing studies have shown that >80 % of the parasite genome is pervasively transcribed in a monocistronic manner during the IDC [ 11 , 12 ], hinting at robust post-transcriptional regulation to fine-tune stage-specific IDC expression. Such a mode of regulation is further supported by an enrichment of genes predicted to encode RNA-binding proteins (RBPs) in the P. falciparum genome [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

The PfAlba1 RNA-binding protein is an important regulator of translational timing in Plasmodium falciparum blood stages

et al. 2015

View full text Add to dashboard Cite

BackgroundTranscriptome-wide ribosome occupancy studies have suggested that during the intra-erythrocytic lifecycle of Plasmodium falciparum, select mRNAs are post-transcriptionally regulated. A subset of these encodes parasite virulence factors required for invading host erythrocytes, and are currently being developed as vaccine candidates. However, the molecular mechanisms that govern post-transcriptional regulation are currently unknown.ResultsWe explore the previously identified DNA/RNA-binding protein PfAlba1, which localizes to multiple foci in the cytoplasm of P. falciparum trophozoites. We establish that PfAlba1 is essential for asexual proliferation, and subsequently investigate parasites overexpressing epitope-tagged PfAlba1 to identify its RNA targets and effects on mRNA homeostasis and translational regulation. Using deep sequencing of affinity-purified PfAlba1-associated RNAs, we identify 1193 transcripts that directly bind to PfAlba1 in trophozoites. For 105 such transcripts, 43 % of which are uncharacterized and 13 % of which encode erythrocyte invasion components, the steady state levels significantly change at this stage, evidencing a role for PfAlba1 in maintaining mRNA homeostasis. Additionally, we discover that binding of PfAlba1 to four erythrocyte invasion mRNAs, Rap1, RhopH3, CDPK1, and AMA1, is linked to translation repression in trophozoites whereas release of these mRNAs from a PfAlba1 complex in mature stages correlates with protein synthesis.ConclusionsWe show that PfAlba1 binds to a sub-population of asexual stage mRNAs and fine-tunes the timing of translation. This mode of post-transcriptional regulation may be especially important for P. falciparum erythrocyte invasion components that have to be assembled into apical secretory organelles in a highly time-dependent manner towards the end of the parasite’s asexual lifecycle.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0771-5) contains supplementary material, which is available to authorized users.

show abstract

“…Deep sequencing of RNA from intraerythrocytic P. falciparum developmental stages has revealed a collection of novel intermediate-size ncRNAs, including novel snoRNAs and unclassified small RNAs. Many of these unclassified RNAs are conserved among different Plasmodium species and are differentially expressed between early and late intraerythrocytic stages [69]. Additionally, a potential novel class of sncRNAs derived from tRNA fragments was revealed in P. falciparum [68].…”

Section: Small Ncrnas In Apicomplexan Parasitesmentioning

confidence: 99%

Noncoding RNAs in Apicomplexan Parasites: An Update

Baptista

Kissinger

2020

Trends in Parasitology

View full text Add to dashboard Cite

Recent breakthroughs in high-throughput technologies, transcriptomics, and advances in our understanding of gene regulatory networks have enhanced our perspective on the complex interplay between parasite and host. Noncoding RNA molecules have been implicated in critical roles covering a broad range of biological processes in the Apicomplexa. Processes that are affected range from parasite development to host-parasite interactions and include interactions with epigenetic machinery and other regulatory factors. Here we review recent progress involving noncoding RNAs and their functions in the Apicomplexa, with a focus on three parasites: Plasmodium, Toxoplasma, and Cryptosporidium. We discuss the limitations and challenges of current methods applied to apicomplexan noncoding RNA study and discuss future directions in this exciting field. The Emerging Importance of ncRNAs With little to no protein-coding capacity, noncoding RNA (ncRNA) (see Glossary) is an essential transcriptome component detected across all domains of life [1]. Although initially considered transcriptional noise (e.g., nonspecific or read-through transcription), ncRNAs have been shown to play critical roles in gene expression regulation at the levels of transcription, RNA processing, and translation [2]. Ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs) were first identified in the 1950s, followed by the discovery of small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs) [2]. The first ncRNAs to be characterized were generally small (b300 nt except for rRNAs), contain stable secondary structure(s), and often operate as components of conserved RNA-protein complexes (Table 1). The ncRNA world blossomed in the early 2000s with advances in sequencing technologies. Since then, various long noncoding RNAs (lncRNAs), microRNA (miRNAs), and more recently tRNA-and snoRNA-derived small ncRNAs (18-40 nt) have been discovered [3,4]. ncRNAs are classified based on transcript length, secondary structure, and genomic and cellular localization [5] (Table 1). The abundance and variety of these molecules has reshaped our understanding of ncRNAs as fundamental transcriptional and post-transcriptional regulators. We emphasize lncRNAs in this review because this class of ncRNA is very heterogeneous and participates in an incredibly diverse set of processes. Most lncRNAs share many similarities with mRNAs, such as RNA polymerase II-mediated transcription, a 5′ 7-methylguanosine cap and a 3′ poly(A) tail [6]. Comparative analyses of lncRNAs reveal that they are not well conserved across species [7,8] and usually have greater tissue-or development-specific expression patterns than mRNAs [9]. By interacting with protein, DNA, or RNA molecules, lncRNAs participate in multiple layers of gene regulation including transcriptional, post-transcriptional, chromatin modification, and nuclear architecture conformation alterations (Box 1). The misregulation of lncRNAs in multicellular eukaryotes has been shown to lead to tumor genesis [10], cardiovascular disease [11], and ...

show abstract

Deep Profiling of the Novel Intermediate-Size Noncoding RNAs in Intraerythrocytic Plasmodium falciparum

Cited by 13 publications

References 60 publications

Trans-acting GC-rich non-coding RNA atvarexpression site modulates gene counting in malaria parasite

Trans-acting GC-rich non-coding RNA atvarexpression site modulates gene counting in malaria parasite

The PfAlba1 RNA-binding protein is an important regulator of translational timing in Plasmodium falciparum blood stages

Noncoding RNAs in Apicomplexan Parasites: An Update

Contact Info

Product

Resources

About