Dataset Information

The Schistosoma mansoni genome encodes thousands of long non-coding RNAs predicted to be functional at different parasite life-cycle stages.

ABSTRACT: Next Generation Sequencing (NGS) strategies, like RNA-Seq, have revealed the transcription of a wide variety of long non-coding RNAs (lncRNAs) in the genomes of several organisms. In the present work we assessed the lncRNAs complement of Schistosoma mansoni, the blood fluke that causes schistosomiasis, ranked among the most prevalent parasitic diseases worldwide. We focused on the long intergenic/intervening ncRNAs (lincRNAs), hidden within the large amount of information obtained through RNA-Seq in S. mansoni (88 libraries). Our computational pipeline identified 7029 canonically-spliced putative lincRNA genes on 2596 genomic loci (at an average 2.7 isoforms per lincRNA locus), as well as 402 spliced lncRNAs that are antisense to protein-coding (PC) genes. Hundreds of lincRNAs showed traits for being functional, such as the presence of epigenetic marks at their transcription start sites, evolutionary conservation among other schistosome species and differential expression across five different life-cycle stages of the parasite. Real-time qPCR has confirmed the differential life-cycle stage expression of a set of selected lincRNAs. We have built PC gene and lincRNA co-expression networks, unraveling key biological processes where lincRNAs might be involved during parasite development. This is the first report of a large-scale identification and structural annotation of lncRNAs in the S. mansoni genome.

SUBMITTER: Vasconcelos EJR

PROVIDER: S-EPMC5585378 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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The Schistosoma mansoni genome encodes thousands of long non-coding RNAs predicted to be functional at different parasite life-cycle stages.

Vasconcelos Elton J R EJR daSilva Lucas F LF Pires David S DS Lavezzo Guilherme M GM Pereira Adriana S A ASA Amaral Murilo S MS Verjovski-Almeida Sergio S

Scientific reports 20170905 1

Next Generation Sequencing (NGS) strategies, like RNA-Seq, have revealed the transcription of a wide variety of long non-coding RNAs (lncRNAs) in the genomes of several organisms. In the present work we assessed the lncRNAs complement of Schistosoma mansoni, the blood fluke that causes schistosomiasis, ranked among the most prevalent parasitic diseases worldwide. We focused on the long intergenic/intervening ncRNAs (lincRNAs), hidden within the large amount of information obtained through RNA-Se ...[more]

PMID: 28874839

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Project description:Long non-coding RNAs (lncRNAs) (>200 nt) are expressed at levels lower than those of the protein-coding mRNAs, and in all eukaryotic model species where they have been characterized, they are transcribed from thousands of different genomic loci. In humans, some four dozen lncRNAs have been studied in detail, and they have been shown to play important roles in transcriptional regulation, acting in conjunction with transcription factors and epigenetic marks to modulate the tissue-type specific programs of transcriptional gene activation and repression. In Schistosoma mansoni, around 10,000 lncRNAs have been identified in previous works. However, the limited number of RNA-sequencing (RNA-seq) libraries that had been previously assessed, together with the use of old and incomplete versions of the S. mansoni genome and protein-coding transcriptome annotations, have hampered the identification of all lncRNAs expressed in the parasite. Here we have used 633 publicly available S. mansoni RNA-seq libraries from whole worms at different stages (n = 121), from isolated tissues (n = 24), from cell-populations (n = 81), and from single-cells (n = 407). We have assembled a set of 16,583 lncRNA transcripts originated from 10,024 genes, of which 11,022 are novel S. mansoni lncRNA transcripts, whereas the remaining 5,561 transcripts comprise 120 lncRNAs that are identical to and 5,441 lncRNAs that have gene overlap with S. mansoni lncRNAs already reported in previous works. Most importantly, our more stringent assembly and filtering pipeline has identified and removed a set of 4,293 lncRNA transcripts from previous publications that were in fact derived from partially processed mRNAs with intron retention. We have used weighted gene co-expression network analyses and identified 15 different gene co-expression modules. Each parasite life-cycle stage has at least one highly correlated gene co-expression module, and each module is comprised of hundreds to thousands lncRNAs and mRNAs having correlated co-expression patterns at different stages. Inspection of the top most highly connected genes within the modules' networks has shown that different lncRNAs are hub genes at different life-cycle stages, being among the most promising candidate lncRNAs to be further explored for functional characterization.

Project description:Schistosoma mansoni is a flatworm that causes schistosomiasis, a neglected tropical disease that affects over 200 million people worldwide. New therapeutic targets are needed with only one drug available for treatment and no vaccine. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein-coding potential. In other organisms, they have been shown as involved with reproduction, stem cell maintenance and drug resistance, and they tend to exhibit tissue-specific expression patterns. S. mansoni expresses thousands of lncRNA genes; however, the cell type expression patterns of lncRNAs in the parasite remain uncharacterized. Here, we have re-analyzed public single-cell RNA-sequencing (scRNA-seq) data obtained from adult S. mansoni to identify the lncRNAs signature of adult schistosome cell types. A total of 8023 lncRNAs (79% of all lncRNAs) was detected. Analyses of the lncRNAs expression profiles in the cells using statistically stringent criteria were performed to identify 74 lncRNA gene markers of cell clusters. Male gamete and tegument lineage clusters contained most of the cluster-specific lncRNA markers. We also identified lncRNA markers of specific neural clusters. Whole-mount in situ hybridization (WISH) and double fluorescence in situ hybridization were used to validate the cluster-specific expression of 13 out of 16 lncRNA gene markers (81%) in the male and female adult parasite tissues; for one of these 16 gene loci, probes for two different lncRNA isoforms were used, which showed differential isoforms usage in testis and ovary. An atlas of the expression profiles across the cell clusters of all lncRNAs detected in our analysis is available as a public website resource. The results presented here give strong support to a tissue-specific expression and to a regulated expression program of lncRNAs in S. mansoni. This will be the basis for further exploration of lncRNA genes as potential therapeutic targets.

Dataset Information

The Schistosoma mansoni genome encodes thousands of long non-coding RNAs predicted to be functional at different parasite life-cycle stages.

Publications

The Schistosoma mansoni genome encodes thousands of long non-coding RNAs predicted to be functional at different parasite life-cycle stages.

Similar Datasets

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