ArticleNature chemical biology2017
Total RNA-seq to identify pharmacological effects on specific stages of mRNA synthesis.
Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- SuppressedInternational journal of molecular sciences · 2026Article
- Transcriptional readthrough precedes alternative splicing programs triggered in CML cells by imatinib.Science advances · 2026Article
- Transcriptional readthrough precedes alternative splicing programs triggered in CML cells by imatinib.bioRxiv : the preprint server for biology · 2025Article
- A multi-tissue atlas of allelic-specific expression reveals the characteristics, mechanisms, and relationship with dominant effects in cattle.BMC biology · 2025Article
- Isoginkgetin Induces Caspase Cascade Activation and Cell Apoptosis via JNK Signaling in Oral Cancer.Journal of Cancer · 2025Article
- Activating transcription factor 4 plays a major role in shaping the transcriptional response to isoginkgetin in HCT116 cells.Scientific reports · 2024Article
- Isoginkgetin and Madrasin are poor splicing inhibitors.PloS one · 2024Article
- Nuclear RNA binding regulates TDP-43 nuclear localization and passive nuclear export.Cell reports · 2022Article
- Splicing modulators: on the way from nature to clinic.The Journal of antibiotics · 2021Review
- Target identification of hepatic fibrosis using Pien Tze Huang based on mRNA and lncRNA.Scientific reports · 2021Article
- Hinokiflavone and Related C-O-C-Type Biflavonoids as Anti-cancer Compounds: Properties and Mechanism of Action.Natural products and bioprospecting · 2021Review
- Enhancers predominantly regulate gene expression during differentiation via transcription initiation.Molecular cell · 2021Article
- GeneWalk identifies relevant gene functions for a biological context using network representation learning.Genome biology · 2021Article
- MeCP2 Represses Enhancers through Chromosome Topology-Associated DNA Methylation.Molecular cell · 2020Article
- MeCP2 Represses the Rate of Transcriptional Initiation of Highly Methylated Long Genes.Molecular cell · 2020Article
- The spliceosome inhibitors isoginkgetin and pladienolide B induce ATF3-dependent cell death.PloS one · 2020Article
- Long and Repeat-Rich Intronic Sequences Favor Circular RNA Formation under Conditions of Reduced Spliceosome Activity.iScience · 2019Article
- Isoginkgetin, a Natural Biflavonoid Proteasome Inhibitor, Sensitizes Cancer Cells to Apoptosis via Disruption of Lysosomal Homeostasis and Impaired Protein Clearance.Molecular and cellular biology · 2019Article
- A Challenging Pie to Splice: Drugging the Spliceosome.Angewandte Chemie (International ed. in English) · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Pharmacological perturbation is a powerful tool for understanding mRNA synthesis, but identification of the specific steps of this multi-step process that are targeted by small molecules remains challenging. Here we applied strand-specific total RNA sequencing (RNA-seq) to identify and distinguish specific pharmacological effects on transcription and pre-mRNA processing in human cells. We found unexpectedly that the natural product isoginkgetin, previously described as a splicing inhibitor, inhibits transcription elongation. Compared to well-characterized elongation inhibitors that target CDK9, isoginkgetin caused RNA polymerase accumulation within a broader promoter-proximal band, indicating that elongation inhibition by isoginkgetin occurs after release from promoter-proximal pause. RNA-seq distinguished isoginkgetin and CDK9 inhibitors from topoisomerase I inhibition, which alters elongation across gene bodies. We were able to detect these and other specific defects in mRNA synthesis at low sequencing depth using simple metagene-based metrics. These metrics now enable total-RNA-seq-based screening for high-throughput identification of pharmacological effects on individual stages of mRNA synthesis.
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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.