mRNAstability

mRNA stability refers to the lifespan of messenger RNA molecules in the cell, defined quantitatively by their half-life. It is a key determinant of gene expression because transcripts that persist longer have more opportunities to be translated, while rapidly degraded mRNAs yield lower protein output. Stability is dynamic and context dependent, varying with cell type, developmental stage, and environmental conditions.

Several features of the mRNA influence stability. Intrinsic elements include the length and sequence of the 5' cap, the coding region, and the poly(A) tail, as well as cis-regulatory motifs in untranslated regions such as AU-rich elements in the 3' UTR. MicroRNAs and RNA-binding proteins bind to specific motifs and can either promote degradation or stabilize transcripts. Trans-acting signals, including signaling pathways and stress responses, remodel the RNA-protein interactome and alter half-lives.

Decay mechanisms commonly involve deadenylation (removal of the poly(A) tail) followed by decapping and exonucleolytic decay from the 5' end by Xrn1 or from the 3' end by the exosome. In some cases, mRNAs are degraded in processing bodies (P-bodies) or through niche pathways such as nonsense-mediated decay if they harbor premature stop codons. Conversely, binding of stabilizing factors can lengthen half-life by inhibiting decay or enhancing translation.

Measurement and relevance: mRNA stability is studied by transcriptional inhibition, metabolic labeling, or sequencing-based approaches to estimate transcript half-lives. Stability influences development, immune responses, and disease, and has implications for therapeutics that aim to modulate transcript levels, including antisense and RNA-targeting technologies.