Modulator-Dependent RBPs Changes Alternative Splicing Outcomes in Kidney Cancer

Yang Wang, Steven X. Chen, Xi Rao, Yunlong Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Alternative splicing alterations can contribute to human disease. The ability of an RNA-binding protein to regulate alternative splicing outcomes can be modulated by a variety of genetic and epigenetic mechanisms. In this study, we use a computational framework to investigate the roles of certain genes, termed modulators, on changing RBPs’ effect on splicing regulation. A total of 1,040,254 modulator-mediated RBP-splicing interactions were identified, including 137 RBPs, 4,309 splicing events and 2,905 modulator candidates from TCGA-KIRC RNA sequencing data. Modulators function categories were defined according to the correlation changes between RBPs expression and their targets splicing outcomes. QKI, as one of the RBPs influencing the most splicing events, attracted our attention in this study: 2,014 changing triplets were identified, including 1,101 modulators and 187 splicing events. Pathway enrichment analysis showed that QKI splicing targets were enriched in tight junction pathway, endocytosis and MAPK signaling pathways, all of which are highly associated with cancer development and progression. This is the first instance of a comprehensive study on how alternative splicing outcomes changes are associated with different expression level of certain proteins, even though they were regulated by the same RBP. Our work may provide a novel view on understanding alternative splicing mechanisms in kidney cancer.

Original languageEnglish (US)
Article number265
JournalFrontiers in Genetics
Volume11
DOIs
StatePublished - Mar 26 2020

Keywords

  • RNA-binding protein
  • alternative splicing
  • cancer
  • dysregulation
  • modulation

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Modulator-Dependent RBPs Changes Alternative Splicing Outcomes in Kidney Cancer'. Together they form a unique fingerprint.

Cite this