CELF1, a Multifunctional Regulator of Posttranscriptional Networks

In order to assure the precise utilization of genetic information, gene expression is regulated at the level of transcription as well as multiple post-transcriptional levels including splicing, transport, localization, mRNA stability, and translation [1],[2],[3],[4],[5],[6],[7]. During evolution, cells developed precise mechanisms to ensure that each transcript is appropriately stored, modified, translated or degraded, depending on the need for the mRNA or encoded protein by the cell. Steady-state protein levels within a cell correlate poorly with steady-state levels of mRNA, leading scientists to hypothesize that the gene expression is regulated at post-transcriptional levels [8]. Work over the past quarter century has resulted in the identification of unifying concepts in post-transcriptional regulation. One unifying concept states is that post-transcriptional regulation is mediated by two major molecular components: cis-acting regulatory sequence elements and trans-acting factors. Cisacting regulatory sequence elements are sub-sequences contained in the 5’ untranslated region (UTR), coding region, and 3’UTR of mRNA that are selectively recognized by a complementary set of one or more trans-acting factors to regulate post-transcriptional gene expression. Trans-acting factors include RNA-binding proteins (RBPs) and microRNAs (miRNAs) which are able to influence the fate of mRNA by controlling processes such as translation and mRNA degradation (reviewed in references [9],[10],[11],[12]). The combinatorial interplay between various miRNAs and RBPs binding to a given mRNA allows for the transcript specific regulation critical to many cellular decisions during development [13],[14],[15],[16] and in response to environmental stimuli (reviewed in references [17],[18],[19],[20],[21],[22]).