ArticleRNA biology2015
Identification of small molecule inhibitors of Zcchc11 TUTase activity.
Article in RNA biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Mutant Huntingtin disrupts neurogenic and astroglial programs via the EZH2-Let-7g-LIN28 axis with rescue by epigenetic modulators.Cell death and differentiation · 2026Article
- Targeting the Lin28/let-7 Axis with Compounds to Regulate Transcriptional Control in Cancer.Anti-cancer agents in medicinal chemistry · 2026Review
- MicroRNA strand ratio disarray promotes temozolomide resistance in glioblastoma.Cellular & molecular biology letters · 2025Article
- RNA Editors Sculpt the Transcriptome During Terminal Erythropoiesis.Research square · 2025Article
- Live cell screening to identify RNA-binding small molecule inhibitors of the pre-let-7-Lin28 RNA-protein interaction.RSC medicinal chemistry · 2024Article
- Cell-based assay to detect small molecules restoring levels of let-7 miRNAs.American journal of cancer research · 2024Article
- The Role of Abnormal Uterine Junction Zone in the Occurrence and Development of Adenomyosis.Reproductive sciences (Thousand Oaks, Calif.) · 2022Review
- METTL1 promotes neuroblastoma development through mBiomarker research · 2022Article
- Review
- NNature communications · 2022Article
- RNA uridyl transferases TUT4/7 differentially regulate miRNA variants depending on the cancer cell type.RNA (New York, N.Y.) · 2022Article
- Identification of novel targets of miR-622 in hepatocellular carcinoma reveals common regulation of cooperating genes and outlines the oncogenic role of zinc finger CCHC-type containing 11.Neoplasia (New York, N.Y.) · 2021Article
- BCDIN3D RNA methyltransferase stimulates Aldolase C expression and glycolysis through let-7 microRNA in breast cancer cells.Oncogene · 2021Article
- Regulation of RNA stability at the 3' end.Biological chemistry · 2021Review
- MicroRNA let-7b downregulates AML1-ETO oncogene expression in t(8;21) AML by targeting its 3'UTR.Experimental hematology & oncology · 2021Article
- Responsive fluorescent nucleotides serve as efficient substrates to probe terminal uridylyl transferase.Chemical communications (Cambridge, England) · 2020Article
- Role of RNA modifications in cancer.Nature reviews. Cancer · 2020Review
- A nanobody targeting the LIN28:let-7 interaction fragment of TUT4 blocks uridylation of let-7.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Crystal structure of the Lin28-interacting module of human terminal uridylyltransferase that regulates let-7 expression.Nature communications · 2019Article
- Genome-wide interaction and pathway-based identification of key regulators in multiple myeloma.Communications biology · 2019Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
The RNA-binding protein Lin28 regulates the expression of the let-7 family of microRNAs (miRNAs) during early embryonic development. Lin28 recruits the 3' terminal uridylyl transferase (TUTase) Zcchc11 (TUT4) and/or Zcchc6 (TUT7) to precursor let-7 RNA (pre-let-7) to selectively block let-7 biogenesis. Uridylated pre-let-7 is targeted for decay by the downstream exonuclease Dis3l2 thereby preventing processing to mature let-7. Activation of this oncogenic pathway via up-regulation of Lin28 expression promotes cellular transformation, drives tumorigenesis in mouse models, and is frequently observed in a wide variety of cancer. Recent proof-of-principle experiments showed that Zcchc11 knockdown inhibits the tumorigenicity of Lin28-expressing human cancer cells and established this enzyme as a possible new therapeutic target for human malignancies. However, there are currently no known pharmacological agents capable of targeting this novel enzyme. In this study we developed and applied a sensitive biochemical assay that monitors Zcchc11 activity. Using this assay we performed an automated high-throughput screen of ∼ 15,000 chemicals to identify putative TUTase inhibitors. Several of these small molecules were validated as specific inhibitors of Zcchc11 activity. Our results demonstrate the feasibility of screening for TUTase inhibitors and present a relatively simple platform that can be exploited for future drug discovery efforts aimed at restoring let-7 expression in cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.