Ontology highlight
ABSTRACT:
PROVIDER: PRJNA834902 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19085875.fastq.gz | Fastqsanger.gz |
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Project description:Background: Sm proteins are multimeric RNA-binding factors, found in all three domains of life. Eukaryotic Sm proteins, together with their associated RNAs, form small ribonucleoprotein (RNP) complexes important in multiple aspects of gene regulation. Comprehensive knowledge of the RNA components of Sm RNPs is critical for understanding their functions. Results: We developed a multi-targeting RNA-immunoprecipitation sequencing (RIP-seq) strategy to reliably identify Sm-associated RNAs from Drosophila ovaries and cultured human cells. Using this method, we discovered three major categories of Sm-associated transcripts: small nuclear (sn)RNAs, small Cajal body (sca)RNAs and mRNAs. Additional RIP-PCR analysis showed both ubiquitous and tissue-specific interactions. We provide evidence that the mRNA-Sm interactions are mediated by snRNPs, and that one of the mechanisms of interaction is via base pairing. Moreover, the Sm-associated mRNAs are mature, indicating a splicing-independent function for Sm RNPs. Conclusions: This study represents the first comprehensive analysis of eukaryotic Sm-containing RNPs, and provides a basis for additional functional analyses of Sm proteins and their associated snRNPs outside of the context of pre-mRNA splicing. Our findings expand the repertoire of eukaryotic Sm-containing RNPs and suggest new functions for snRNPs in mRNA metabolism.
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Project description:Antigen-specific regulatory T cells (Tregs) suppress pathogenic autoreactivity and are potential therapeutic candidates for autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis is associated with autoreactivity to the Smith (Sm) autoantigen and the human leucocyte antigen (HLA)-DR15 haplotype; hence, we investigated the potential of Sm-specific Tregs (Sm-Tregs) to suppress disease. We identified a novel HLA-DR15 restricted immunodominant Sm T cell epitope using biophysical affinity binding assays, then identified high-affinity Sm-specific T cell receptors (TCRs) using high-throughput single-cell sequencing. Using lentiviral vectors, we transduced our lead Sm-specific TCR onto Tregs derived from patients with SLE who were anti-Sm and HLA-DR15 positive. Compared with polyclonal mock-transduced Tregs, Sm-Tregs potently suppressed Sm-specific pro-inflammatory responses in vitro and suppressed disease progression in a humanized mouse model of lupus nephritis. These results show that Sm-Tregs are a promising therapy for SLE.
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Project description:Samul-tang (SM), a traditional herbal medicine is used to treat menstrual irregularities and infertility. The mechanism underlying the role of SM in ovary function needs elucidation. In this study, the influence of SM administration on the ovarian reserve of aged mice was investigated. Female BALB/c mice (8 and 40 weeks-old) were administered with distilled water (young or old group) or SM for 4 weeks. SM administration prevented age-related ovarian follicle loss in mice. Quality of oocytes and blastocysts were enhanced in SM-administrated mice compared to those of non-treated old mice. Further, SM administration increased the pregnancy rate and number of litters. SM triggered changes in aging-related genes that are linked to the RAS-mediated pathway. Thus, we demonstrate that SM can be used to increase the oocyte yield in aged women, potentially improving age-related cognitive decline in the ovarian reserve.
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Project description:Ramariopsis corniculata, genomic and transcriptomic data
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