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      Genome-Wide Identification of Schistosoma japonicum MicroRNAs Using a Deep-Sequencing Approach

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          Abstract

          Background

          Human schistosomiasis is one of the most prevalent and serious parasitic diseases worldwide. Schistosoma japonicum is one of important pathogens of this disease. MicroRNAs (miRNAs) are a large group of non-coding RNAs that play important roles in regulating gene expression and protein translation in animals. Genome-wide identification of miRNAs in a given organism is a critical step to facilitating our understanding of genome organization, genome biology, evolution, and posttranscriptional regulation.

          Methodology/Principal Findings

          We sequenced two small RNA libraries prepared from different stages of the life cycle of S. japonicum, immature schistosomula and mature pairing adults, through a deep DNA sequencing approach, which yielded ∼12 million high-quality short sequence reads containing a total of ∼2 million non-redundant tags. Based on a bioinformatics pipeline, we identified 176 new S. japonicum miRNAs, of which some exhibited a differential pattern of expression between the two stages. Although 21 S. japonicum miRNAs are orthologs of known miRNAs within the metazoans, some nucleotides at many positions of Schistosoma miRNAs, such as miR-8, let-7, miR-10, miR-31, miR-92, miR-124, and miR-125, are indeed significantly distinct from other bilaterian orthologs. In addition, both miR-71 and some miR-2 family members in tandem are found to be clustered in a reversal direction model on two genomic loci, and two pairs of novel S. japonicum miRNAs were derived from sense and antisense DNA strands at the same genomic loci.

          Conclusions/Significance

          The collection of S. japonicum miRNAs could be used as a new platform to study the genomic structure, gene regulation and networks, evolutionary processes, development, and host-parasite interactions. Some S. japonicum miRNAs and their clusters could represent the ancestral forms of the conserved orthologues and a model for the genesis of novel miRNAs.

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          Most cited references25

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          Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing.

          RNAi is a gene-silencing phenomenon triggered by double-stranded (ds) RNA and involves the generation of 21 to 26 nt RNA segments that guide mRNA destruction. In Caenorhabditis elegans, lin-4 and let-7 encode small temporal RNAs (stRNAs) of 22 nt that regulate stage-specific development. Here we show that inactivation of genes related to RNAi pathway genes, a homolog of Drosophila Dicer (dcr-1), and two homologs of rde-1 (alg-1 and alg-2), cause heterochronic phenotypes similar to lin-4 and let-7 mutations. Further we show that dcr-1, alg-1, and alg-2 are necessary for the maturation and activity of the lin-4 and let-7 stRNAs. Our findings suggest that a common processing machinery generates guide RNAs that mediate both RNAi and endogenous gene regulation.
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            Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans.

            We sequenced approximately 400,000 small RNAs from Caenorhabditis elegans. Another 18 microRNA (miRNA) genes were identified, thereby extending to 112 our tally of confidently identified miRNA genes in C. elegans. Also observed were thousands of endogenous siRNAs generated by RNA-directed RNA polymerases acting preferentially on transcripts associated with spermatogenesis and transposons. In addition, a third class of nematode small RNAs, called 21U-RNAs, was discovered. 21U-RNAs are precisely 21 nucleotides long, begin with a uridine 5'-monophosphate but are diverse in their remaining 20 nucleotides, and appear modified at their 3'-terminal ribose. 21U-RNAs originate from more than 5700 genomic loci dispersed in two broad regions of chromosome IV-primarily between protein-coding genes or within their introns. These loci share a large upstream motif that enables accurate prediction of additional 21U-RNAs. The motif is conserved in other nematodes, presumably because of its importance for producing these diverse, autonomously expressed, small RNAs (dasRNAs).
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              Reassessment of the cost of chronic helmintic infection: a meta-analysis of disability-related outcomes in endemic schistosomiasis.

              Schistosomiasis is one of the world's most prevalent infections, yet its effect on the global burden of disease is controversial. Published disability-adjusted life-year (DALY) estimates suggest that the average effect of schistosome infection is quite small, although this is disputed. To develop an evidenced-based reassessment of schistosomiasis-related disability, we did a systematic review of data on disability-associated outcomes for all forms of schistosomiasis. We did structured searches using EMBASE, PUBMED, and Cochrane electronic databases. Published bibliographies were manually searched, and unpublished studies were obtained by contacting research groups. Reports were reviewed and abstracted independently by two trained readers. All randomised and observational studies of schistosomiasis morbidity were eligible for inclusion. We calculated pooled estimates of reported disability-related effects using weighted odds ratios for categorical outcomes and standardised mean differences for continuous data. 482 published or unpublished reports (March, 1921, to July, 2002) were screened. Of 135 selected for inclusion, 51 provided data for performance-related symptoms, whereas 109 reported observed measures of disability-linked morbidities. Schistosomiasis was significantly associated with anaemia, chronic pain, diarrhoea, exercise intolerance, and undernutrition. By contrast with WHO estimates of 0.5% disability weight assigned to schistosomiasis, 2-15% disability seems evident in different functional domains of a person with schistosomiasis. This raised estimate, if confirmed in formal patient-preference studies, indicates a need to reassess our priorities for treating this silent pandemic of schistosomiasis.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2009
                8 December 2009
                : 4
                : 12
                : e8206
                Affiliations
                [1 ]Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China
                [2 ]Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
                [3 ]National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China
                Sabin Vaccine Institute, United States of America
                Author notes

                Conceived and designed the experiments: JH ZGH. Performed the experiments: JH HC. Analyzed the data: JH ZGH. Contributed reagents/materials/analysis tools: PH WH FL. Wrote the paper: JH ZGH. Constructed the website used in the study: QY.

                Article
                09-PONE-RA-10856R2
                10.1371/journal.pone.0008206
                2785426
                19997615
                f9af892c-49b8-486a-b6f0-8a679691e849
                Huang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 6 June 2009
                : 9 November 2009
                Page count
                Pages: 9
                Categories
                Research Article
                Genetics and Genomics
                Infectious Diseases
                Non-Clinical Medicine

                Uncategorized
                Uncategorized

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