Structure and Genomic Organization of the Human AUF1 Gene: Alternative Pre-mRNA Splicing Generates Four Protein Isoforms

Wagner, B.; DeMaria, Christine T.; Sun, Yue; Wilson, Gerald M.; Brewer, Gary

doi:10.1006/geno.1997.5142

Cited by 259 publications

(252 citation statements)

References 29 publications

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“…The probe protected by AUF1 mRNA including or lacking the beginning of Exon 3'b is 237 or 66 nt long, respectively Several isoforms of AUF1 exist which are due to alternative pre-mRNA splicing (Wagner et al, 1998): two alternative exons occur in the coding region, one encoding a 19-aa insert located at the beginning of RRM1; the other one encoding a 49-aa insert located near the glutamine-rich domain (see Figure 3A and Ehrenman et al, 1994;Kajita et al, 1995). Because of their location and coding potential, these exons alter AUF1 a nity and speci®city (Kajita et al, 1995;Wagner et al, 1998) making their relative accumulation important to determine. Using speci®c probes, we have analysed the pattern of expression of several AUF1 isoforms (+49+19 and +19+49) and found that whatever the isoform considered, the highest level of expression was observed in lymphoid tissues and the lowest in the liver.…”

Section: Discussionmentioning

confidence: 99%

“…(b) ECL detection after incubation with anti-AUF1 antibodies AUF1, HuR and c-myc mRNA expression in vivo I Lafon et al 1995; Zhang et al, 1993) revealed two in frame insertions, one 57 bp long in the 5' coding region and another, 147 bp long, in the 3' coding region ( Figure 3A). These variations, which result from alternative pre-mRNA splicing (Wagner et al, 1998), lead either to a 19 amino-acid (19-aa) insertion in the N-terminal portion of RRM1 or to a 49-amino acid (49-aa) insertion in the C-terminal region of the AUF1 isoforms, respectively (see Figure 3A). The presence of isoform-speci®c mRNAs can thus explain the presence of native proteins with di erent apparent molecular masses.…”

Section: Complexity Of Auf1 Mrnasmentioning

confidence: 99%

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Developmental expression of AUF1 and HuR, two c-myc mRNA binding proteins

et al. 1998

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Several proteins that may regulate c-myc mRNA posttranscriptionally were previously isolated and characterized. Two of them, HuR and AUF1, bind speci®cally to the 3' untranslated region (UTR) of c-myc mRNA. Because c-myc is regulated post-transcriptionally in various mouse tissues, including quiescent tissues, fetal liver and regenerating liver, we investigated whether HuR and AUF1 expression was also regulated in these tissues. Concerning AUF1, we analysed the expression of various mRNA and protein isoforms. We discovered a new AUF1 mRNA variant with a long AU-rich 3' UTR. We show that AUF1 expression, regardless of the RNA isoform considered, and HuR mRNA expression parallel c-myc expression in quiescent tissues and during liver development; their expression is high in lymphoid tissues and fetal liver and low in adult liver. However, no upregulation of HuR or AUF1 accompanies the upregulation of c-myc mRNA following partial hepatectomy. We discuss our results in relation to the current hypothesis that HuR and AUF1 act as mRNA destabilizing factors.

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Section: Discussionmentioning

confidence: 99%

Section: Complexity Of Auf1 Mrnasmentioning

confidence: 99%

Developmental expression of AUF1 and HuR, two c-myc mRNA binding proteins

et al. 1998

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“…Briefly, AUF1 encodes for a family of four isoforms generated by alternative splicing denoted by their apparent molecular weights as p37 AUF1 , p40 AUF1 , p42 AUF1 , and p45 AUF1 (Wagner et al, 1998). Normally, the p42 and p45 isoforms appear exclusively in the nucleus (Zhang et al, 1993;Arao et al, 2000).…”

Section: Auf1mentioning

confidence: 99%

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

Bevilacqua

Ceriani

Capaccioli

et al. 2003

Journal Cellular Physiology

294

259

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Recent evidence suggests that gene expression may be regulated, at least in part, at post-transcriptional level by factors inducing the extremely rapid degradation of messenger RNAs. These factors include reactions between adenyl-uridyl-rich elements (AREs) of the relevant mRNA and either specific proteins that bind to these elements or exosomes. This review deals with examples of the proteins (AU-rich binding proteins, AUBPs) and exosomes, which have been shown to form complexes with AREs and bring about rapid degradation of the relevant mRNA, and with certain other factors, which protect the RNA from such degradation. The biochemical and physiological factors underlying the stability of messenger RNAs carrying the ARE motifs will be reviewed in the light of their emerging significance for cell physiology, human pathology, and molecular medicine. We also consider the possible application of the results of recent insights into the mechanisms to pharmacological interventions to prevent or cure disorders, especially developmental disorders, which the suppression of gene expression may bring about. Molecular targeting of specific steps in protein degradation by synthetic compounds has already been utilized for the development of pharmacological therapies.

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“…111 Sequential dimer binding causes local remodeling and condensation of the mRNA substrate. 112,113 Through alternative splicing, AUF1 is expressed as 37, 40, 42 and 45 kDa isoforms 114 (Figure 2). The p45 isoform contains 19 amino acids coded by exon 2 and 49 amino acids coded by exon 7; p42 contains exon 7; p40 contains exon 2 and p37 contains neither.…”

Section: Destabilizing Proteinsmentioning

confidence: 99%

mRNA stability control: a clandestine force in normal and malignant hematopoiesis

Steinman

2007

Leukemia

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This review addresses the scope of influence of mRNA decay on cellular functions and its potential role in normal and malignant hematopoiesis. Evidence is emerging that leukemic oncogenes and hematopoietic cytokines interact with mRNA decay pathways. These pathways can co-regulate functionally related genes through specific motifs in the 3 0 -untranslated region of targeted transcripts. The steps that link external stimuli to transcript turnover are not fully understood, but include subcellular relocalization or post-transcriptional modification of specific transcript-stabilizing or -destabilizing proteins. Improper functioning of these regulators of mRNA turnover can impede normal cellular differentiation or promote cancers. By delineating how subsets of transcripts decay in synchrony during normal hematopoiesis, it may be possible to determine whether this post-transcriptional regulatory pathway is hijacked in leukemogenesis.

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Structure and Genomic Organization of the Human AUF1 Gene: Alternative Pre-mRNA Splicing Generates Four Protein Isoforms

Cited by 259 publications

References 29 publications

Developmental expression of AUF1 and HuR, two c-myc mRNA binding proteins

Developmental expression of AUF1 and HuR, two c-myc mRNA binding proteins

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

mRNA stability control: a clandestine force in normal and malignant hematopoiesis

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