AUF1 regulation of coding and noncoding RNA.
AUF1 is a family of four RNA-binding proteins (RBPs) generated by alternative pre-messenger RNA (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 microRNA (miRNA)-loaded RNA-induced silencing complexes (miRISCs), miRISC targeting to mRNA substrates, interplay with an expanding network of other cellular RBPs, 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. WIREs RNA 2017, 8:e1393. doi: 10.1002/wrna.1393 For further resources related to this article, please visit the WIREs website.
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA.|Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Elizabeth J F
EJ
White
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA.|Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Aerielle E
AE
Matsangos
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA.|Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Gerald M
GM
Wilson
D000818:Animals; D005786:Gene Expression Regulation; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D012322:RNA Precursors / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism
C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D012322:RNA Precursors; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D016601:RNA-Binding Proteins