Comprehensive Schistosoma mansoni Hierarchical Transcriptome Assembly Points to Novel lncRNAs Associated with Sexual Dimorphism.

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-Coding RNA Pub Date : 2026-03-12 DOI:10.3390/ncrna12020009

Caio Felipe Freire, Thalles Souza-Lopes, Murilo Sena Amaral, Ana Carolina Tahira, Sergio Verjovski-Almeida

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引用次数: 0

Abstract

Background/Objectives: Schistosomiasis is a neglected tropical disease affecting >200 million people worldwide. Praziquantel is the sole recommended drug against Schistosoma mansoni; however, it lacks activity against juvenile forms and cannot prevent reinfection. Thus, there is an urgent need to identify novel therapeutic targets. Long noncoding RNAs (lncRNAs) are known to regulate various biological processes in S. mansoni, including parasite pairing and fertility; therefore, screening for novel lncRNAs could reveal new potential targets. Methods: We compiled all publicly available RNA-seq data from the Sequence Read Archive (SRA) and performed a hierarchical transcriptome assembly using the multi-sample assembler Ryūtō, combined with version 10 of the S. mansoni genome. We applied HOMER for peak-calling and identification of histone marks and used weighted gene co-expression network analysis (WGCNA) to infer putative functions of lncRNAs in sexual dimorphism. Results: Using a robust pipeline, we identified 10,170 novel lncRNA genes comprising 16,990 novel lncRNA transcripts, including 8783 intergenic, 7918 antisense, and 289 intronic lncRNA transcripts. Most (78.7%) have histone regulatory marks (H3K4me3, H3K27me3, H3K27ac, or H4K20me1) near their transcription start sites, indicating potential expression regulation. Comparing male and female samples, we identified 1991 differentially expressed genes (FDR < 5%, |log₂FC| ≥ 1.5), including 296 known lncRNAs and 339 novel lncRNAs. WGCNA identified hub lncRNAs within co-expression modules, and Gene Ontology enrichment analyses (FDR ≤ 5%) suggest that these lncRNAs are involved in cell differentiation and morphogenesis pathways. Conclusions: We provide a comprehensive catalog of S. mansoni lncRNAs. These findings offer opportunities to discover potential new therapeutic targets, advancing the future development of anti-schistosome therapies.

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全面的曼氏血吸虫分层转录组组装指向与性别二态性相关的新型lncrna。

背景/目的：血吸虫病是一种被忽视的热带病，影响全世界2亿人。吡喹酮是唯一推荐的抗曼氏血吸虫药物；然而，它缺乏对幼虫的活性，不能防止再感染。因此，迫切需要确定新的治疗靶点。已知长链非编码rna （lncRNAs）调控mansoni的各种生物过程，包括寄生虫配对和繁殖；因此，筛选新的lncrna可以揭示新的潜在靶点。方法：我们从序列读取档案（SRA）中编译了所有公开可用的RNA-seq数据，并使用多样本汇编器Ryūtō结合mansoni基因组版本10进行了分层转录组组装。我们使用HOMER进行组蛋白标记的峰值识别和鉴定，并使用加权基因共表达网络分析（WGCNA）推断lncrna在两性二态性中的推测功能。结果：通过一个强大的管道，我们鉴定了10,170个新的lncRNA基因，包括16,990个新的lncRNA转录本，包括8783个基因间转录本，7918个反义转录本和289个内含子lncRNA转录本。大多数（78.7%）在转录起始位点附近有组蛋白调控标记（H3K4me3、H3K27me3、H3K27ac或H4K20me1），表明可能存在表达调控。比较男性和女性样本，我们发现了1991个差异表达基因（FDR < 5%, |log2FC|≥1.5），包括296个已知lncrna和339个新lncrna。WGCNA鉴定出共表达模块中的枢纽lncrna，基因本体富集分析（FDR≤5%）表明这些lncrna参与细胞分化和形态发生途径。结论：我们提供了一个完整的mansoni lncrna目录。这些发现为发现潜在的新治疗靶点提供了机会，推动了抗血吸虫疗法的未来发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

6.70

自引率

4.70%

发文量

审稿时长

10 weeks

期刊介绍： Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.