Emerging roles of spliceosome in cancer and immunity

Protein Cell. 2022 Aug;13(8):559-579. doi: 10.1007/s13238-021-00856-5. Epub 2021 Jul 1.

Abstract

Precursor messenger RNA (pre-mRNA) splicing is catalyzed by an intricate ribonucleoprotein complex called the spliceosome. Although the spliceosome is considered to be general cell "housekeeping" machinery, mutations in core components of the spliceosome frequently correlate with cell- or tissue-specific phenotypes and diseases. In this review, we expound the links between spliceosome mutations, aberrant splicing, and human cancers. Remarkably, spliceosome-targeted therapies (STTs) have become efficient anti-cancer strategies for cancer patients with splicing defects. We also highlight the links between spliceosome and immune signaling. Recent studies have shown that some spliceosome gene mutations can result in immune dysregulation and notable phenotypes due to mis-splicing of immune-related genes. Furthermore, several core spliceosome components harbor splicing-independent immune functions within the cell, expanding the functional repertoire of these diverse proteins.

Keywords: cancer; immune dysregulation; innate immunity; spliceosome; splicing.

Publication types

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

MeSH terms

  • Humans
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • RNA Precursors / genetics
  • RNA Precursors / metabolism
  • RNA Splicing
  • RNA Splicing Factors / genetics
  • RNA Splicing Factors / metabolism
  • Spliceosomes* / genetics
  • Spliceosomes* / metabolism

Substances

  • RNA Precursors
  • RNA Splicing Factors