Coordinate regulation of mRNA decay networks by GU-rich elements and CELF1

The GU-rich element (GRE) was identified as a conserved sequence enriched in the 3′ UTR of human transcripts that exhibited rapid mRNA turnover. In mammalian cells, binding to GREs by the protein CELF1 coordinates mRNA decay of networks of transcripts involved in cell growth, migration, and apoptosis. Depending on the context, GREs and CELF1 also regulate pre-mRNA splicing and translation. GREs are highly conserved throughout evolution and play important roles in the development of organisms ranging from worms to man. In humans, abnormal GRE-mediated regulation contributes to disease states and cancer. Thus, GREs and CELF proteins serve critical functions in gene expression regulation and define an important evolutionarily conserved posttranscriptional regulatory network.

► The GU-rich element (GRE) is enriched in transcripts that decay rapidly.
► The protein CELF1 mediates mRNA decay by binding to GREs.
► GREs regulate multiple transcripts involved in cell activation and development.
► Abnormal GRE-mediated regulation contributes to disease states and cancer.
► GREs and CELF1 define an evolutionarily conserved regulatory network.