AUF1 regulation of coding and noncoding RNA : AUF1 regulation of coding and noncoding RNA

Abstract

<p class="first" id="P1">AUF1 is a family of four RNA-binding proteins generated by alternative pre-mRNA splicing, with canonical roles in controlling the stability and/or translation of mRNA targets based on recognition of AU-rich sequences within mRNA 3′ untranslated regions. However, recent studies identifying AUF1 target sites across the transcriptome have revealed that these canonical functions are but a subset of its roles in posttranscriptional regulation of gene expression. In this review, we describe recent developments in our understanding of the RNA-binding properties of AUF1 together with their biochemical implications and roles in directing mRNA decay and translation. This is then followed by a survey of newly discovered activities for AUF1 proteins in control of miRNA synthesis and function, including miRNA assembly into miRISC complexes, miRISC targeting to mRNA substrates, interplay with an expanding network of other cellular RNA-binding proteins, and reciprocal regulatory relationships between miRNA and AUF1 synthesis. Finally, we discuss recently reported relationships between AUF1 and long noncoding RNAs and regulatory roles on viral RNA substrates. Cumulatively, these findings have significantly expanded our appreciation of the scope and diversity of AUF1 functions in the cell, and are prompting an exciting array of new questions moving forward. </p><p id="P2"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/fcc45420-996d-4c48-babd-822a48a376ae/PubMedCentral/image/nihms811939u1.jpg"/> </div> </p><p id="P3">AUF1 enhances loading of select miRNAs into RISC complexes but can also regulate miRISC access to mRNA substrates. </p>