Adenylate-uridylate-rich element-containing messenger RNAs (ARE-mRNAs)

Adenylate-uridylate-rich element-containing messenger RNAs (ARE-mRNAs) are a class of transcripts characterized by the presence of specific AU-rich sequences, typically located in their 3' untranslated regions (3' UTRs). These elements serve as critical cis-acting signals that dictate the half-life and translation efficiency of the mRNA by recruiting various RNA-binding proteins (RBPs), such as HuR, which stabilizes the transcript, or Tristetraprolin (TTP), which promotes its rapid degradation. ARE-mRNAs frequently encode potent biological mediators including pro-inflammatory cytokines (e.g., TNF-alpha, IL-1, IL-6), growth factors, and proto-oncogenes (e.g., c-Myc, Cyclin D1), making their tight regulation essential for cellular homeostasis. In many pathological states, particularly oncology and chronic inflammatory diseases, the ARE-mediated decay pathway is subverted, leading to the stabilization and overexpression of disease-driving proteins. For instance, the overexpression of the stabilizing protein HuR in many cancers leads to the persistent expression of survival and proliferative factors. Therapeutic strategies targeting ARE-mRNAs often focus on small molecules that disrupt the interaction between these transcripts and their cognate RBPs. By promoting the degradation of stabilized ARE-mRNAs, these therapies aim to reduce the levels of oncogenic or inflammatory proteins at the post-transcriptional level, offering a distinct approach from traditional transcriptional or enzymatic inhibition.

Other names

AU-rich element-containing mRNAsARE-containing transcriptsAU-rich elementsAREs

Modulation of mRNA stability and translation by interfering with the binding of RNA-binding proteins (RBPs) to AU-rich elements, thereby promoting degradation or inhibiting the stabilization of specific transcripts.