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

Abstract

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.

LFA-1-Dependent HuR Nuclear Export and Cytokine mRNA Stabilization in T Cell Activation

“…It is possible that LFA-1-mediated signals, notably resulting in HuR translocation and consequential RNA stabilization, are more effectively targeted to class II rather than class I sequences. This idea seems unlikely, as HuR has been shown, in fact, to bind the 3Ј-UTR of c-myc RNA (36). Rather, there are multiple cis-elements within the c-myc transcript that are degradation targets and control its half-life, including sequences within the 5Ј-UTR, as well as within exons 2 and 3 (37).…”

Synchronous and regulated expression of two AU-binding proteins, AUF1 and HuR, throughout murine development

“…The signal detected by the AUF1 probe corresponds to RNAs encoding all four isoforms (Lafon et al, 1998). Speci®c signals were detected with each probe as early as E8.5 (data not shown).…”

“…However, the functions of HuR and AUF1 in cell proliferation and dierentiation have yet to be investigated. Although proposed to be ubiquitous, expression of these proteins has been reported only in a small number of experiments performed with dierentiated cells, either from tissue culture (Lo¯in et al, 1999), adult tissues (Ma et al, 1996;Lafon et al, 1998) or tumours (Nabors et al, 1998). Thus our knowledge of their developmental expression remains very limited.…”

“…ND, D: undigested or digested respectively; P: protected probe decided to compare its pattern of expression to that of AUF1 and HuR proteins at dierent developmental stages and in dierent tissues. All together, the analyses performed either by in situ hybridization on wholemount E10.5 embryos (Figure 1) or at later stage by S1 nuclease protection assay ( Figure 6 and Lafon et al, 1998;Morello et al, 1989) indicate that, in most circumstances, its expression follows that of AUF1 and HuR.…”

The role of AUF1 in thyroid carcinoma progression

“…However, in cells capable of proliferation such as fetal hepatocytes and adult lymphocytes, where AUF1 levels are much higher compared with adult hepatocytes, it could protect c-myc mRNA from decay (Lafon et al 1998). Current data in transgenic mice showed that overexpression of AUF1 followed by deregulation of c-myc, c-fos, and c-jun led to the development of sarcomas with strong cyclin D1 expression.…”