Emerging Evidence of Translational Control by AU-Rich Element-Binding Proteins

Conclusion and Perspectives The ARE has been studied for a long time, and about 20 ARE-BPs have been identified since discovery of first ARE-BP, AUF1 (Brewer, 1991; Garcia-Maurino et al., 2017). The specific target mRNAs for different ARE-BPs, as well as their molecular functions on these mRNAs, and contribution of this regulation to specific biological processes are gradually being uncovered. However, with a few exceptions, the molecular mechanisms used by ARE-BPs to regulate their targets are still unknown. In particular, the mechanism to recognize and control specific targets from the large number of transcripts that have AREs is an open question. Recently, Ball et al. revealed that ZFP36L2, but not ZFP36L1, recognizes one of three AREs in 3′UTR of mRNA coding LHR, and this ARE is located within a hairpin structure (Ball et al., 2014, 2017). This indicates that not only the ARE sequence but also proximal RNA secondary structure affects the binding specificity of ARE-BPs. Future experimental and in silico approaches to understand the determinants of ARE recognition by specific ARE-BPs’ analysis will thus be needed to incorporate RNA structure, as well as sequence. Moreover, as shown in the example of LDHM and AUF1 (Pioli et al., 2002), it will also be necessary to study the influence of the interaction between ARE-BPs on specific ARE recognition and molecular regulatory mechanisms on the same transcripts. Finally, systematic studies have sho...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research

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