Human DBR1 modulates the recycling of snRNPs to affect alternative RNA splicing and contributes to the suppression of cancer development

Oncogene. 2017 Sep 21;36(38):5382-5391. doi: 10.1038/onc.2017.150. Epub 2017 May 15.


The contribution of RNA processing to tumorigenesis is understudied. Here, we report that the human RNA debranching enzyme (hDBR1), when inappropriately regulated, induces oncogenesis by causing RNA processing defects, for example, splicing defects. We found that wild-type p53 and hypoxia-inducible factor 1 co-regulate hDBR1 expression, and insufficient hDBR1 leads to a higher rate of exon skipping. Transcriptomic sequencing confirmed the effect of hDBR1 on RNA splicing, and metabolite profiling supported the observation that neoplasm is triggered by a decrease in hDBR1 expression both in vitro and in vivo. Most importantly, when modulating the expression of hDBR1, which was found to be generally low in malignant human tissues, higher expression of hDBR1 only affected exon-skipping activity in malignant cells. Together, our findings demonstrate previously unrecognized regulation and functions of hDBR1, with immediate clinical implications regarding the regulation of hDBR1 as an effective strategy for combating human cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Cell Hypoxia / physiology
  • Cell Line, Tumor
  • Exons
  • Humans
  • Hypoxia-Inducible Factor 1 / genetics
  • Hypoxia-Inducible Factor 1 / metabolism
  • Introns
  • Neoplasms / enzymology
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • RNA Nucleotidyltransferases / biosynthesis*
  • RNA Nucleotidyltransferases / genetics
  • RNA Nucleotidyltransferases / metabolism
  • RNA Splicing
  • Ribonucleoproteins, Small Nuclear / genetics
  • Ribonucleoproteins, Small Nuclear / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism


  • Hypoxia-Inducible Factor 1
  • Ribonucleoproteins, Small Nuclear
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Dbr1 protein, human
  • RNA Nucleotidyltransferases