Regulation of RNA Splicing: Aberrant Splicing Regulation and Therapeutic Targets in Cancer

Cells. 2021 Apr 16;10(4):923. doi: 10.3390/cells10040923.

Abstract

RNA splicing is a critical step in the maturation of precursor mRNA (pre-mRNA) by removing introns and exons. The combination of inclusion and exclusion of introns and exons in pre-mRNA can generate vast diversity in mature mRNA from a limited number of genes. Cancer cells acquire cancer-specific mechanisms through aberrant splicing regulation to acquire resistance to treatment and to promote malignancy. Splicing regulation involves many factors, such as proteins, non-coding RNAs, and DNA sequences at many steps. Thus, the dysregulation of splicing is caused by many factors, including mutations in RNA splicing factors, aberrant expression levels of RNA splicing factors, small nuclear ribonucleoproteins biogenesis, mutations in snRNA, or genomic sequences that are involved in the regulation of splicing, such as 5' and 3' splice sites, branch point site, splicing enhancer/silencer, and changes in the chromatin status that affect the splicing profile. This review focuses on the dysregulation of RNA splicing related to cancer and the associated therapeutic methods.

Keywords: RNA splicing; aberrant splicing; cancer; non-coding RNA; splicing factor; splicing variant; treatment targeting splicing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Molecular Targeted Therapy*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics*
  • RNA Splicing / genetics*
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism

Substances

  • RNA, Untranslated