Genome Biology: The 3′ end of the story: deciphering combinatorial interactions that control mRNA fate.

Precise control of messenger RNA (mRNA) fate—its translation, stability, and localization—is required for accurate eukaryotic gene expression and is of fundamental importance to human health and disease. Initial efforts to determine how the cell controls these processes focused on “who done it?” We now understand that many of the clues required to answer this question reside in the mRNA’s 3′ untranslated region. For example, the cis-regulatory elements embedded in the 3′ untranslated region engage trans-acting microRNAs (miRNAs) and RNA-binding proteins (RBPs). RBPs and miRNAs package the message into ribonucleoprotein particles (messenger ribonucleoprotein particles, mRNPs) that are remodeled throughout the life cycle of the mRNA. Like transcription factors, these post-transcriptional regulators control the abundance of the message as well as its association with the translation machinery, and therefore dictate the protein output of a gene.

Until recently, attempts to unravel the regulatory impact of RBPs and miRNAs focused on interrogating one of the usual suspects in isolation, using genomic or molecular approaches that provide snapshots of transient interaction sites. Individual and group efforts like ENCODE produced catalogs of these interactions. However, more often than not, these regulatory factors collaborate in unexpected ways to control post-transcriptional gene expression. Therefore, there is a need to develop strategies that allow us to dissect cross-talk among regulators and link…