ArticleMolecular cell2018
The Augmented R-Loop Is a Unifying Mechanism for Myelodysplastic Syndromes Induced by High-Risk Splicing Factor Mutations.
Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 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
195 citing papers in PubMed, 318 citations in OpenAlex.
- A phase 1b/2 study of ceralasertib, a selective inhibitor of ATR, in patients with relapsed or refractory MDS and CMML.Blood advances · 2026Trial
- Clinical presentation and differential splicing of SRSF2, U2AF1 and SF3B1 mutations in patients with acute myeloid leukemia.Leukemia · 2020Trial
- Sensitivity to ATR-CHK1 pathway inhibition in MDS/AML is enhanced by SRSF2 mutations and reduced by RUNX1 loss.Leukemia · 2026Article
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- SRSF2 P95H induces monocytic priming of human hematopoietic stem and progenitor cells.Leukemia · 2026Article
- The insulin/IGF axis is critically important for controlling gene transcription in the podocyte.eLife · 2026Article
- R-loops in colorectal cancer: mechanisms, mapping strategies, and therapeutic opportunities.Molecular biology reports · 2026Review
- PANoptosis in the pathogenesis of myelodysplastic syndromes.Molecular oncology · 2026Review
- Nonsense-Mediated RNA Decay Is a Targetable Vulnerability in Splicing Factor Mutant Myeloid Neoplasms by Enhancing R-Loop Accumulation and DNA Damage.Cancer research · 2026Article
- R-loops and D-loops: a delicate balance in genomic stability and instability.Cell communication and signaling : CCS · 2026Review
- Splicing-driven post-translational dysregulation: a new frontier for precision cancer medicine and immunotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Multi-omics dissection of R-loop dynamics in tumorigenesis: From transcription-replication conflict to therapeutic targets.Molecular therapy. Oncology · 2026Review
- Outstanding Questions to Understand and Target Splicing Factor-Mutant Blood Cancers.Blood cancer discovery · 2026Article
- Integrator 20th anniversary: a molecular machine indispensable in development and disease.Trends in molecular medicine · 2026Review
- Integrative Analysis Reveals Conserved R-Loop Features in Mouse Embryonic Stem Cells.Epigenomes · 2026Article
- R-loops orchestrate RNAPII transcriptional reprogramming for the maternal-to-zygotic transition.Cell research · 2026Article
- Regulation of transcription by R loop-nucleated transcription condensate assembly.Cell & bioscience · 2026Review
- Vulnerability of SRSF2-mutated chronic myelomonocytic leukemia to perturbation of the cGAS-STING pathway.Blood advances · 2026Article
- SRSF3-TRIM28-MDC1 prevents DNA damage caused by R-loops in fatty liver disease in mice.JCI insight · 2026Article
- Alternative nucleic acid structures in microbial biology: regulatory functions and antimicrobial opportunities.Frontiers in cellular and infection microbiology · 2026Review
135 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Mutations in several general pre-mRNA splicing factors have been linked to myelodysplastic syndromes (MDSs) and solid tumors. These mutations have generally been assumed to cause disease by the resultant splicing defects, but different mutations appear to induce distinct splicing defects, raising the possibility that an alternative common mechanism is involved. Here we report a chain of events triggered by multiple splicing factor mutations, especially high-risk alleles in SRSF2 and U2AF1, including elevated R-loops, replication stress, and activation of the ataxia telangiectasia and Rad3-related protein (ATR)-Chk1 pathway. We further demonstrate that enhanced R-loops, opposite to the expectation from gained RNA binding with mutant SRSF2, result from impaired transcription pause release because the mutant protein loses its ability to extract the RNA polymerase II (Pol II) C-terminal domain (CTD) kinase-the positive transcription elongation factor complex (P-TEFb)-from the 7SK complex. Enhanced R-loops are linked to compromised proliferation of bone-marrow-derived blood progenitors, which can be partially rescued by RNase H overexpression, suggesting a direct contribution of augmented R-loops to the MDS phenotype.
Indexed as
Identifiers
What OpenQuestion holds
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.