CUG-repeat binding protein 1 (CUGBP1) mediates selective mRNA decay by binding to GU-rich elements (GREs) containing the sequence UGUUUGUUUGU found in the 3 untranslated region (UTR) of short-lived transcripts. We used an anti-CUGBP1 antibody to immunoprecipitate CUGBP1 from HeLa cytoplasmic extracts and analyzed the associated transcripts using oligonucleotide microarrays. We identified 613 putative mRNA targets of CUGBP1 and found that the UGUUUGUUUGU GRE sequence and a GU-repeat sequence were both highly enriched in the 3 UTRs of these targets. We showed that CUGBP1 bound specifically to the GU-repeat sequence and that insertion of this sequence into the 3 UTR of a beta-globin reporter transcript conferred instability to the transcript. Based on these results, we redefined the GRE to include this GU-repeat sequence. Our results suggest that CUGBP1 coordinately regulates the mRNA decay of a network of transcripts involved in cell growth, cell motility, and apoptosis.

SUMMARY T cell receptor (TCR) cross-reactivity between major histocompatibility complex II (MHCII)-binding self and foreign peptides could influence the naïve CD4+ T cell repertoire and autoimmunity. We found that nonamer peptides that bind to the same MHCII molecule only need to share five amino acids to cross-react on the same TCR. This property was biologically relevant since systemic expression of a self peptide reduced the size of a naïve cell population specific for a related foreign peptide by deletion of cells with cross-reactive TCRs. Reciprocally, an incompletely deleted naïve T cell population specific for a tissue-restricted self peptide could be triggered by related microbial peptides to cause autoimmunity. Thus, TCR cross-reactivity between similar self and foreign peptides can reduce the size of certain foreign peptide-specific T cell populations, and may allow T cell populations specific for tissue-restricted self peptides to cause autoimmunity after infection.

Background:We identified target transcripts of the RNA-binding protein CUGBP1 in resting and activated T cells. Results: T cell activation induced CUGBP1 phosphorylation, causing decreased CUGBP1 binding to target transcripts. Conclusion: CUGBP1 binding to a network of target transcripts is regulated by CUGBP1 phosphorylation following T cell activation. Significance: CUGBP1 target transcripts are coordinately regulated during T cell activation.

Table 1 of this paper published in the January 2015 issue contains several errors. The Derp1 peptide comes from the Der p1 protein of Dermatophagoides pteronyssinus not the Der f1 protein of Dermatophagoides farinae. The sequence of the MOG peptide in the I-A b tetramer used in the study was GWYRSPFSRVV not GWYRSPFSRVVVHLY. The most likely 9 amino acid core register for the OVA2C peptide in the I-A b tetramer used in the study is VHAAHAEIN not AVHAAHAEI, which is the second most likely. The most likely register has a different number of predicted self peptide homologs than the second most likely one, which changed the x axis value for the OVA2C peptide in Figure 4G. However, neither the level of statistical significance of the correlation between the number of self peptide homologs and the number of naive cells specific for foreign peptides shown in Figure 4G nor the conclusion that ''TCR cross-reactivity on self-peptide homologs plays some role in determining the size of MHCII-bound foreign peptide-specific CD4 + T cell populations'' were changed. Thus, none of these errors affect any of the conclusions of the paper. The authors deeply regret these errors and apologize for them. Corrected versions of the table and figure appear here.

The AU-rich element (ARE) was discovered in 1986 as a conserved mRNA sequence found in the 3′ untranslated region of the TNF-α transcript and other transcripts encoding cytokines and inflammatory mediators. Shortly thereafter, the ARE was shown to function as a regulator of mRNA degradation, and AREs were later shown to regulate other posttranscriptional mechanisms such as translation and mRNA localization. AREs coordinately regulate networks of chemokine, cytokine, and growth regulatory transcripts involved in cellular activation, proliferation, and inflammation. ARE-mediated regulation is carried out by a host of ARE-binding proteins, whose activity is regulated in a cell type and activation-dependent manner. The last 25 years of ARE research has offered insight into the mechanisms and regulation of ARE-mediated mRNA decay, and has provided a road map for the discovery of additional mRNA regulatory motifs. The future of ARE research will transition from a discovery phase to a phase focused on translating basic biological findings into novel therapeutic targets. Our understanding of ARE-mediated gene regulation and posttranscriptional control has implications for many fields of study including developmental biology, neuroscience, immunobiology, and cancer biology.

Our data identify suppression of fibroblast Dicer1 expression in the myofibroblast-rich IPF fibroblastic focus core as a central step in the mechanism by which the ECM sustains fibrosis progression in IPF.

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