Unknown

Dataset Information

0

Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs.


ABSTRACT: DNA-methyltransferase inhibitors (DNMTis), such as azacitidine and decitabine, are used clinically to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Decitabine activates the transcription of endogenous retroviruses (ERVs), which can induce immune response by acting as cellular double-stranded RNAs (dsRNAs). Yet, the posttranscriptional regulation of ERV dsRNAs remains uninvestigated. Here, we find that the viral mimicry and subsequent cell death in response to decitabine require the dsRNA-binding protein Staufen1 (Stau1). We show that Stau1 directly binds to ERV RNAs and stabilizes them in a genome-wide manner. Furthermore, Stau1-mediated stabilization requires a long noncoding RNA TINCR, which enhances the interaction between Stau1 and ERV RNAs. Analysis of a clinical patient cohort reveals that MDS and AML patients with lower Stau1 and TINCR expressions exhibit inferior treatment outcomes to DNMTi therapy. Overall, our study reveals the posttranscriptional regulatory mechanism of ERVs and identifies the Stau1-TINCR complex as a potential target for predicting the efficacy of DNMTis and other drugs that rely on dsRNAs.

SUBMITTER: Ku Y 

PROVIDER: S-EPMC8020767 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

2021-04-14 | GSE152258 | GEO
| S-EPMC6667616 | biostudies-literature
| S-EPMC5361811 | biostudies-literature
2022-06-09 | PXD016019 | Pride
| S-EPMC9220180 | biostudies-literature
| PRJNA638824 | ENA
2015-12-31 | E-GEOD-45538 | biostudies-arrayexpress
| S-EPMC8191804 | biostudies-literature
| S-EPMC9016899 | biostudies-literature
| S-EPMC2725788 | biostudies-literature