Alternative Splicing in Apicomplexan Parasites

Yeoh, Lee M.; Lee, V Vern; McFadden, Geoffrey I.; Ralph, Stuart A.

doi:10.1128/mbio.02866-18

Cited by 25 publications

(24 citation statements)

References 107 publications

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“…Alternative splicing can regulate gene expression in signal dependent and tissue-specific manners 38 and an emerging body of evidence links alternative splicing with the control of circadian regulatory networks in a variety of organisms, including Drosophila melanogaster 39 , Neurospora crassa 40,41 , Arabidopsis 42,43 , and Mus musculus 44 . Alternative splicing has been reported to occur in Apicomplexans (including malaria parasites) for relatively few genes, covering only several percent of the total genes 45 .…”

Section: Sr10 Affects Rhythmic Expression Of Spliceosome Machinerymentioning

confidence: 99%

Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms

et al. 2020

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Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24 h suggesting a circadian basis, but the mechanism controlling this periodicity is unknown. Combining in vivo and in vitro approaches utilizing rodent and human malaria parasites, we reveal that: (i) 57% of Plasmodium chabaudi genes exhibit daily rhythms in transcription; (ii) 58% of these genes lose transcriptional rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 6% of Plasmodium falciparum genes show 24 h rhythms in expression under free-running conditions; (iv) Serpentine receptor 10 (SR10) has a 24 h transcriptional rhythm and disrupting it in rodent malaria parasites shortens the IDC by 2-3 h; (v) Multiple processes including DNA replication, and the ubiquitin and proteasome pathways, are affected by loss of coordination with host rhythms and by disruption of SR10. Our results reveal malaria parasites are at least partly responsible for scheduling the IDC and coordinating their development with host daily rhythms.

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Section: Sr10 Affects Rhythmic Expression Of Spliceosome Machinerymentioning

confidence: 99%

Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms

et al. 2020

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“…Notably, the increase in intron number and its retention correlates strongly with multicellular complexity (as defined by numbers of distinct cell types) [72,73]. In apicomplexans, the splicing machinery appears to be largely conserved but features of gene structure such as intron number, length and distribution can be highly variable [18]. In our study, the difference in intron number between T. gondii and P. falciparum is a relevant example.…”

Section: Discussionmentioning

confidence: 60%

“…Although alternative splicing appears to play a major (though debated) role in posttranscriptional control in metazoans, the process in less understood in apicomplexans. Studies have identified apicomplexan genes with crucial alternative splicing outcomes [18]. For example, alternative splicing is required for attaching a protein trafficking pre-sequence onto two adjacent gene coding sequences [19], and normal multi-organellar targeting of the P. falciparum cysteinyl tRNA synthetase, which is essential for parasite survival [20].…”

Section: Introductionmentioning

confidence: 99%

Direct nanopore sequencing of mRNA reveals landscape of transcript isoforms in apicomplexan parasites

Lee

Judd

Jex

et al. 2020

Preprint

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Alternative splicing is a widespread phenomenon in metazoans by which single genes are able to produce multiple isoforms of the gene product. However, this has been poorly characterised in apicomplexans, a major phylum of some of the most important global parasites. Efforts have been hampered by atypical transcriptomic features, such as the high AT content of Plasmodium RNA, but also the limitations of short read sequencing in deciphering complex splicing events. In this study, we utilised the long read direct RNA sequencing platform developed by Oxford Nanopore Technologies (ONT) to survey the alternative splicing landscape of Toxoplasma gondii and Plasmodium falciparum. We find that while native RNA sequencing has a reduced throughput, it allows us to obtain full-length or near full-length transcripts with comparable quantification to Illumina sequencing. By comparing this data with available gene models, we find widespread alternative splicing, particular intron retention, in these parasites. Most of these transcripts contain premature stop codons, suggesting that in these parasites, alternative splicing represents a pathway to transcriptomic diversity, rather than expanding proteomic diversity. Moreover, alternative splicing rates are comparable between parasites, suggesting a shared splicing machinery, despite notable transcriptomic differences between the parasites. This work highlights a strategy in using long read sequencing to understand splicing events at the whole transcript level, and has implications in future interpretation of RNA-seq studies.

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“…In turn, a better understanding of the biology of T. parva transmission, colonization and pathogenesis may ultimately reveal novel targets for pathogen control [14]. Currently, much like for other apicomplexan parasites [15,16] , 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 5 knowledge on the functional role of genomic sequences outside of T. parva CDSs is sparse, and many gene models containing only CDSs are supported by little or no experimental evidence. RNAseq data, generated through deep sequencing of cDNA using next generation sequencing technologies, can provide an extraordinary level of insight into gene structure and regulation [12,17].…”

Section: Manuscriptmentioning

confidence: 99%

Re-annotation of the Theileria parva genome refines 53% of the proteome and uncovers essential components of N-glycosylation, a conserved pathway in many organisms

Tretina

Pellé

Orvis

et al. 2019

Preprint

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AbstractBackgroundThe apicomplexan parasite Theileria parva causes a livestock disease called East coast fever (ECF), with millions of animals are at risk in sub-Saharan East and Southern Africa, the geographic distribution of T. parva. Over a million bovines die each year of ECF, with a tremendous economic burden to pastoralists in endemic countries. Comprehensive, accurate parasite genome annotation can facilitate the discovery of novel chemotherapeutic targets for disease treatment, as well as elucidate the biology of the parasite. However, genome annotation remains a significant challenge because of limitations in the quality and quantity of the data being used to inform the location and function of protein-coding genes and, when RNA data are used, the underlying biological complexity of the processes involved in gene expression. Here, we apply our recently published RNAseq dataset derived from the schizont life-cycle stage of T. parva to update structural and functional gene annotations across the entire nuclear genome.ResultsThe re-annotation effort lead to evidence-supported updates in over half of all protein-coding sequence (CDS) predictions, including exon changes, gene merges and gene splitting, an increase in average CDS length of approximately 50 base pairs, and the identification of 128 new genes. Among the new genes identified were those involved in N-glycosylation, a process previously thought not to exist in this organism and a potentially new chemotherapeutic target pathway for treating ECF. Alternatively-spliced genes were identified, and antisense and multi-gene family transcription were extensively characterized.ConclusionsThe process of re-annotation led to novel insights into the organization and expression profiles of protein-coding sequences in this parasite, and uncovered a minimal N-glycosylation pathway that changes our current understanding of the evolution of this post-translation modification in apicomplexan parasites.

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Alternative Splicing in Apicomplexan Parasites

Abstract: Alternative splicing is a widespread, essential, and complex component of gene regulation. Apicomplexan parasites have long been recognized to produce alternatively spliced transcripts for some genes and can produce multiple protein products that are essential for parasite growth.

Cited by 25 publications

References 107 publications

Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms

Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms

Direct nanopore sequencing of mRNA reveals landscape of transcript isoforms in apicomplexan parasites

Re-annotation of the Theileria parva genome refines 53% of the proteome and uncovers essential components of N-glycosylation, a conserved pathway in many organisms

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