Alternative mRNA processing sites decrease genetic variability while increasing functional diversity.

Recent large-scale RNA sequencing efforts have revealed the extensive diversity of mRNA molecules produced from most eukaryotic coding genes, which arises from the usage of alternative, cryptic or non-canonical splicing and intronic polyadenylation sites. The prevailing view regarding the tremendous diversity of coding gene transcripts is that mRNA processing is a flexible and more-or-less noisy process leading to a diversity of proteins on which natural selection can act depending on protein-mediated cellular functions. However, this concept raises two main questions. First, do alternative mRNA processing pathways have a role other than generating mRNA and protein diversity? Second, is the cellular function of mRNA variants restricted to the biogenesis of functional protein isoforms? Here, I propose that the co-transcriptional use of alternative mRNA processing sites allows first, the resolution of co-transcriptional biophysical constraints that may otherwise result in DNA instability, and second, increases the diversity of cellular functions of mRNAs in a manner that is not restricted to protein synthesis.