The question how the expression of eukaryotic protein-coding genes is regulated in response to developmental or environmental cues has fascinated many generations of researchers. Intuitively one would expect that the formation of mRNA by transcription is the crucial event in gene expression regulation and indeed many examples of this type of regulation have been described in the past. However, discoveries in recent years have emphasized that post-transcriptional mechanisms also have profound effects on gene expression. No matter whether these mechanisms occur co- or post-transcriptionally, they ultimately regulate protein synthesis, either directly, by affecting the rate of translation, or indirectly, by affecting the half-life or localization of mRNA.
mRNA is made available for the translation machinery only after several post-transcriptional steps, including the proper processing of mRNA precursors, correct transport and localization to and within the cytoplasm. Diverse processes including translational silencing or controlled decay, on the other hand, limits its availability. Studies of recent years have shown that mRNAs at all stages of their life interact with trans-acting factors, including proteins and various non-coding RNA, to serve their functions in gene expression. Importantly, because there are many mRNA-interacting factors and each mRNA is the blueprint of a particular protein, the resulting ribonucleoprotein particles (mRNPs) are unique in their composition. This gives rise to the “mRNP code” concept, which implies that specific sets of proteins, non-coding RNAs and other molecules bind to individual mRNAs and control their fate and function in every cell. As many of the mRNP-associated factors become recruited, re-organized and released according to specific needs in the mRNA’s life cycle, the code is highly dynamic and reflects the functional status of each mRNA.
The compositions of mRNPs as a bulk entity has been studied in some detail and several RNA binding proteins (RBPs) and their interaction sites on mRNA have been identified. However, insight into how the mRNP code manifests itself on individual transcripts and is read by the cell has remained limited. With the recent technical advances in the high-throughput analysis of proteins and RNAs, the investigation of the mRNP composition of specific mRNAs and its functional relevance has become feasible.