ArticleBMC cell biology2013
THOC5, a member of the mRNA export complex, contributes to processing of a subset of wingless/integrated (Wnt) target mRNAs and integrity of the gut epithelial barrier.
Article in BMC cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 27 citations in OpenAlex.
- Cannabidiol triggers fatty acids β-oxidation mediated by Stat2 to facilitate intestinal stem cells regeneration post radiation.Experimental & molecular medicine · 2026Article
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- Application of genetic risk score for in-stent restenosis of second- and third-generation drug-eluting stents in geriatric patients.BMC geriatrics · 2023Article
- THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate.iScience · 2023Article
- Comprehensive Analysis of the Expression and Clinical Significance of THO Complex Members in Hepatocellular Carcinoma.International journal of general medicine · 2022Article
- Genetic risk model for in-stent restenosis of second-and third-generation drug-eluting stents.iScience · 2021Article
- Article
- The THO Complex Coordinates Transcripts for Synapse Development and Dopamine Neuron Survival.Cell · 2018Article
- The role of TREX in gene expression and disease.The Biochemical journal · 2016Review
- Depletion of three combined THOC5 mRNA export protein target genes synergistically induces human hepatocellular carcinoma cell death.Oncogene · 2016Article
- Nuclear export of messenger RNA.Genes · 2015Review
- Murine precision-cut liver slices (PCLS): a new tool for studying tumor microenvironments and cell signaling ex vivo.Cell communication and signaling : CCS · 2014Article
- THOC5 controls 3'end-processing of immediate early genes via interaction with polyadenylation specific factor 100 (CPSF100).Nucleic acids research · 2014Article
- THOC5, a member of the mRNA export complex: a novel link between mRNA export machinery and signal transduction pathways in cell proliferation and differentiation.Cell communication and signaling : CCS · 2014Review
- The Thoc1 encoded ribonucleoprotein is required for myeloid progenitor cell homeostasis in the adult mouse.PloS one · 2014Article
- THOC5 regulates human osteoclastogenesis.European journal of cell biologyArticle
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTHO (Suppressors of the transcriptional defects of hpr1 delta by overexpression) complex 5 (THOC5), an mRNA export protein, is involved in the expression of only 1% of all genes. Using an interferon inducible knockout mouse system, we have previously shown that THOC5 is an essential element in the maintenance of hematopoietic stem cells and cytokine-mediated hematopoiesis in adult mice. Here we interrogate THOC5 function in cell differentiation beyond the hematopoietic system and study pathological changes caused by THOC5 deficiency.
resultsTo examine whether THOC5 plays a role in general differentiation processes, we generated tamoxifen inducible THOC5 knockout mice. We show here that the depletion of THOC5 impaired not only hematopoietic differentiation, but also differentiation and self renewal of the gut epithelium. Depletion of the THOC5 gene did not cause pathological alterations in liver or kidney. We further show that THOC5 is indispensable for processing of mRNAs induced by Wnt (wingless/integrated) signaling which play key roles in epithelial cell differentiation/proliferation. A subset of Wnt target mRNAs, SRY-box containing gene 9 (Sox9), and achaete-scute complex homolog 2 (Ascl2), but not Fibronectin 1 (Fn1), were down-regulated in THOC5 knockout intestinal cells. The down-regulated Wnt target mRNAs were able to bind to THOC5. Furthermore, pathological alterations in the gastrointestinal tract induced translocation of intestinal bacteria and caused sepsis in mice. The bacteria translocation may cause Toll-like receptor activation. We identified one of the Toll-like receptor inducible genes, prostaglandin-endoperoxidase synthase 2 (Ptgs2 or COX2) transcript as THOC5 target mRNA.
conclusionTHOC5 is indispensable for processing of only a subset of mRNAs, but plays a key role in processing of mRNAs inducible by Wnt signals. Furthermore, THOC5 is dispensable for general mRNA export in terminally differentiated organs, indicating that multiple mRNA export pathways exist. These data imply that THOC5 may be a useful tool for studying intestinal stem cells, for modifying the differentiation processes and for cancer therapy.
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