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Physiological networks and disease functions of RNA ‐binding protein AUF1
Author(s) -
Moore Ashleigh E.,
Chenette Devon M.,
Larkin Lauren C.,
Schneider Robert J.
Publication year - 2014
Publication title -
wiley interdisciplinary reviews: rna
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.225
H-Index - 71
eISSN - 1757-7012
pISSN - 1757-7004
DOI - 10.1002/wrna.1230
Subject(s) - messenger rna , rna binding protein , untranslated region , biology , post transcriptional regulation , gene expression , microbiology and biotechnology , translation (biology) , regulation of gene expression , gene isoform , three prime untranslated region , rna splicing , au rich element , rna , alternative splicing , gene , genetics
Regulated messenger RNA ( mRNA ) decay is an essential mechanism that governs proper control of gene expression. In fact, many of the most physiologically potent proteins are encoded by short‐lived mRNAs , many of which contain AU ‐rich elements ( AREs ) in their 3′‐untranslated region (3′‐ UTR ). AREs target mRNAs for post‐transcriptional regulation, generally rapid decay, but also stabilization and translation inhibition. AREs control mRNA turnover and translation activities through association with trans ‐acting RNA ‐binding proteins that display high affinity for these AU ‐rich regulatory elements. AU ‐rich element RNA ‐binding protein ( AUF1 ), also known as heterogeneous nuclear ribonucleoprotein D ( HNRNPD ), is an extensively studied AU ‐rich binding protein ( AUBP ). AUF1 has been shown to regulate ARE‐mRNA turnover, primarily functioning to promote rapid ARE‐mRNA degradation. In certain cellular contexts, AUF1 has also been shown to regulate gene expression at the translational and even the transcriptional level. AUF1 comprises a family of four related protein isoforms derived from a common pre‐ mRNA by differential exon splicing. AUF1 isoforms have been shown to display multiple and distinct functions that include the ability to target ARE‐mRNA stability or decay, and transcriptional activation of certain genes that is controlled by their differential subcellular locations, expression levels, and post‐translational modifications. AUF1 has been implicated in controlling a variety of physiological functions through its ability to regulate the expression of numerous mRNAs containing 3′‐ UTR AREs , thereby coordinating functionally related pathways. This review highlights the physiological functions of AUF1 ‐mediated regulation of mRNA and gene expression, and the consequences of deficient AUF1 levels in different physiological settings. WIREs RNA 2014, 5:549–564. doi: 10.1002/wrna.1230 This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes RNA Turnover and Surveillance > Regulation of RNA Stability RNA in Disease and Development > RNA in Disease