Post-Transcriptional Regulation of Anti-Apoptotic BCL2 Family Members

Int J Mol Sci. 2018 Jan 20;19(1):308. doi: 10.3390/ijms19010308.

Abstract

Anti-apoptotic B cell lymphoma 2 (BCL2) family members (BCL2, MCL1, BCLxL, BCLW, and BFL1) are key players in the regulation of intrinsic apoptosis. Dysregulation of these proteins not only impairs normal development, but also contributes to tumor progression and resistance to various anti-cancer therapies. Therefore, cells maintain strict control over the expression of anti-apoptotic BCL2 family members using multiple mechanisms. Over the past two decades, the importance of post-transcriptional regulation of mRNA in controlling gene expression and its impact on normal homeostasis and disease have begun to be appreciated. In this review, we discuss the RNA binding proteins (RBPs) and microRNAs (miRNAs) that mediate post-transcriptional regulation of the anti-apoptotic BCL2 family members. We describe their roles and impact on alternative splicing, mRNA turnover, and mRNA subcellular localization. We also point out the importance of future studies in characterizing the crosstalk between RBPs and miRNAs in regulating anti-apoptotic BCL2 family member expression and ultimately apoptosis.

Keywords: RNA binding proteins; alternative splicing; anti-apoptotic BCL2 subfamily; apoptosis; mRNA stability; mRNA subcellular localization; microRNA; post-transcriptional regulation.

Publication types

  • Review

MeSH terms

  • Alternative Splicing
  • Animals
  • Apoptosis / genetics*
  • Gene Expression Regulation, Neoplastic
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Humans
  • MicroRNAs / genetics
  • Multigene Family*
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA Processing, Post-Transcriptional*
  • RNA Stability
  • RNA Transport
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism

Substances

  • Heterogeneous-Nuclear Ribonucleoproteins
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • RNA-Binding Proteins