Multiple roles for AU-rich RNA binding proteins in the development of haematologic malignancies and their resistance to chemotherapy

RNA Biol. 2024 Jan;21(1):1-17. doi: 10.1080/15476286.2024.2346688. Epub 2024 May 27.


Post-transcriptional regulation by RNA binding proteins can determine gene expression levels and drive changes in cancer cell proteomes. Identifying mechanisms of protein-RNA binding, including preferred sequence motifs bound in vivo, provides insights into protein-RNA networks and how they impact mRNA structure, function, and stability. In this review, we will focus on proteins that bind to AU-rich elements (AREs) in nascent or mature mRNA where they play roles in response to stresses encountered by cancer cells. ARE-binding proteins (ARE-BPs) specifically impact alternative splicing, stability, decay and translation, and formation of RNA-rich biomolecular condensates like cytoplasmic stress granules (SGs). For example, recent findings highlight the role of ARE-BPs - like TIAR and HUR - in chemotherapy resistance and in translational regulation of mRNAs encoding pro-inflammatory cytokines. We will discuss emerging evidence that different modes of ARE-BP activity impact leukaemia and lymphoma development, progression, adaptation to microenvironment and chemotherapy resistance.

Keywords: AU-rich element; RNA binding protein; RNA stability; cellular stress; chemotherapy resistance; leukaemia; lymphoma; microenvironment; pre-mRNA splicing; stress granules.

Publication types

  • Review

MeSH terms

  • AU Rich Elements
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Drug Resistance, Neoplasm* / genetics
  • Gene Expression Regulation, Neoplastic
  • Hematologic Neoplasms* / drug therapy
  • Hematologic Neoplasms* / genetics
  • Hematologic Neoplasms* / metabolism
  • Humans
  • Protein Binding
  • RNA Stability
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism


  • RNA-Binding Proteins
  • RNA, Messenger
  • Antineoplastic Agents