mRNA degradation

• PUF-binding motifs and AU-rich elements (AREs) in 3'-untranslated region (UTR) and CG di-nucleotides in the 5′-UTR accelerated mRNA decay
• Using microarrays we compiled a database of mRNA degradation rates in mouse ES cells (19977 genes).
• Unstable mRNA species are enriched in regulatory genes (transcription factors, signal transduction, cell cycle), and stable mRNA species are enriched in structural genes and genes associated with metabolism
• Number of exons per ORF length was the strongest predictor of mRNA degradation rate, indicating that exon junctions increase mRNA stability.
• ARE (AU-rich elements) in 3′UTR negatively affected mRNA stability; sequence non-specific AREs had a stronger effect than sequence-specific AREs
• CG elements in 5′UTR negatively affected mRNA stability
• Differentiation of ES cells after LIF withdrawal decreased average mRNA stability, whereas differentiation induced by RA resulted in increased average stability
• There was no global relation between changes in mRNA stability and gene expression in ES cells upon differentiation 

1. Different mRNAs within the same cell have distinct lifetimes (stabilities). In bacterial cells, individual mRNAs can survive from seconds to more than an hour; in mammalian cells, mRNA lifetimes range from several minutes to days. The greater the stability of an mRNA the more protein may be produced from that mRNA
2. Inside eukaryotic cells, there is a balance between the processes of translation and mRNA decay
3. eIF-4E and eIF-4G block the decapping enzyme (DCP2), and poly(A)-binding protein blocks the exosome complex, protecting the ends of the message
4. The presence of AU-rich elements in some mammalian mRNAs tends to destabilize those transcripts through the action of cellular proteins that bind these sequences and stimulate poly(A) tail removal
5. Binding of a miRNA to a message can repress translation of that message and accelerate poly(A) tail removal, thereby hastening mRNA degradation