Functional screens identify coordinators of RNA molecule birth, life, and death as targetable cancer vulnerabilities

Curr Opin Genet Dev. 2019 Feb:54:105-109. doi: 10.1016/j.gde.2019.04.003. Epub 2019 May 20.

Abstract

RNA molecules are subject to a complex co-transcriptional and post-transcriptional life cycle, controlled at all stages by RNA binding proteins (RBPs) and non-coding RNAs that influence mRNA stability, splicing, localization, and decay. Together with mechanisms regulating the process of transcription itself, non-coding RNAs and RBPs contribute to a model of para-transcriptional coordination of gene expression, which is utilized during normal tissue physiology and cancer development in order to execute complex gene expression programs. Several key regulators of RNA biology, such as certain splice factors, represent bona fide cancer vulnerabilities, but our understanding of these processes is still far away from being comprehensive. Genetic forward screens utilizing technologies such as transposons, RNAi and CRISPR aid the field in rapidly establishing functional phenotypes and genetic cancer cell addictions. This review focuses on four individual regulatory gene expression processes governed by regulators of the RNA life cycle, the impact of functional genomics on streamlining the discovery process and the role of such mechanisms in tumor biology.

Publication types

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

MeSH terms

  • Animals
  • CRISPR-Cas Systems / genetics*
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Mice
  • Neoplasms / genetics*
  • RNA / genetics
  • RNA Stability / genetics*
  • RNA, Untranslated / genetics*
  • RNA-Binding Proteins / genetics

Substances

  • RNA, Untranslated
  • RNA-Binding Proteins
  • RNA