AUTHOR=García-Mauriño Sofía M. , Rivero-Rodríguez Francisco , Velázquez-Cruz Alejandro , Hernández-Vellisca Marian , Díaz-Quintana Antonio , De la Rosa Miguel A. , Díaz-Moreno Irene TITLE=RNA Binding Protein Regulation and Cross-Talk in the Control of AU-rich mRNA Fate JOURNAL=Frontiers in Molecular Biosciences VOLUME=4 YEAR=2017 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2017.00071 DOI=10.3389/fmolb.2017.00071 ISSN=2296-889X ABSTRACT=

mRNA metabolism is tightly orchestrated by highly-regulated RNA Binding Proteins (RBPs) that determine mRNA fate, thereby influencing multiple cellular functions across biological contexts. Here, we review the interplay between six well-known RBPs (TTP, AUF-1, KSRP, HuR, TIA-1, and TIAR) that recognize AU-rich elements (AREs) at the 3′ untranslated regions of mRNAs, namely ARE-RBPs. Examples of the links between their cross-regulations and modulation of their targets are analyzed during mRNA processing, turnover, localization, and translational control. Furthermore, ARE recognition can be self-regulated by several factors that lead to the prevalence of one RBP over another. Consequently, we examine the factors that modulate the dynamics of those protein-RNA transient interactions to better understand the final consequences of the regulation mediated by ARE-RBPs. For instance, factors controlling the RBP isoforms, their conformational state or their post-translational modifications (PTMs) can strongly determine the fate of the protein-RNA complexes. Moreover, mRNA specific sequence and secondary structure or subtle environmental changes are also key determinants to take into account. To sum up, the whole understanding of such a fine tuned regulation is a challenge for future research and requires the integration of all the available structural and functional data by in vivo, in vitro and in silico approaches.