Translation and the stability of mRNAs encoding the transferrin receptor and c-fos.

  title={Translation and the stability of mRNAs encoding the transferrin receptor and c-fos.},
  author={David M. Koeller and J A Horowitz and John L Casey and Richard D. Klausner and Joe B Harford},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  volume={88 17},
  • D. Koeller, J. Horowitz, J. Harford
  • Published 1 September 1991
  • Biology
  • Proceedings of the National Academy of Sciences of the United States of America
Turnover of the full-length human transferrin receptor (TfR) mRNA is regulated by iron, and this regulation is mediated by the transcript's 3' untranslated region. Alterations in the sequence of the TfR mRNA regulatory region have been identified that render the mRNA unregulated by iron and intrinsically unstable. When cells expressing this unstable mRNA are treated with inhibitors of protein synthesis (cycloheximide or puromycin), the steady-state level of the encoded human TfR mRNA is… 
Characterization of the Translation-dependent Step during Iron-regulated Decay of Transferrin Receptor mRNA*
Observations suggest that inhibition of translation by cycloheximide interferes with the rate-limiting step of iron-induced TfR mRNA decay in a trans-acting mechanism by blocking IRP inactivation.
Effect of Transcription Inhibitors on the Iron-dependent Degradation of Transferrin Receptor mRNA *
It is demonstrated that part of the active IRP co-localizes with TfR mRNA to the rough endoplasmic reticulum, indicating that IRP dissociates prior to T fR mRNA decay.
Multiple instability-regulating sites in the 3' untranslated region of the urokinase-type plasminogen activator mRNA
All chimeric unstable globin mRNAs became stable in the presence of cycloheximide, a protein synthesis inhibitor, suggesting that the stabilization of mRNA by protein synthesis inhibition is not through a specific sequence in the mRNA.
Selective degradation of early-response-gene mRNAs: functional analyses of sequence features of the AU-rich elements
The hypothesis that the c-fos ARE-directed mRNA decay is a two-step mechanism in which rapid shortening of the poly(A) tail leads to the decay of the mRNA body is proposed and it is hypothesized that this is a general mechanism by which the ERG AREs mediate rapid mRNA degradation.
Post-Transcriptional Considerations of Gene Expression: Translation, MRNA Stability, and Poly(A) Processing
It is demonstrated that achieving optimal synthesis of a recombinant protein might not be as simple as linking a transcriptional promoter to an open reading frame; considerations concerning the effects of RNA splicing, 3′ end formation/polyadenylation, RNA localization, translation and stability of the cytoplasmic mRNA and protein all influence the production of a protein.
mRNA decay mediated by two distinct AU-rich elements from c-fos and granulocyte-macrophage colony-stimulating factor transcripts: different deadenylation kinetics and uncoupling from translation
It is reported that two structurally different AREs, the c-fos ARE and the granulocyte-macrophage colony-stimulating factor ARE, both direct rapid deadenylation as the first step in mRNA degradation, but by different kinetics.
Evidence for instability of mRNAs containing AUUUA motifs mediated through translation-dependent assembly of a > 20S degradation complex.
It is proposed that RNA instability mediated by the AU motif is achieved through translation-dependent assembly of this large mRNA-destabilizing complex found only on unstable RNAs.
Selective destabilization of short-lived mRNAs with the granulocyte-macrophage colony-stimulating factor AU-rich 3' noncoding region is mediated by a cotranslational mechanism
It is demonstrated that mRNAs which are poorly translated through the introduction of stable secondary structure in the 5' noncoding region are not efficiently targeted for selective destabilization by the (AUUUA)n element, suggesting that AUUUA-mediated degradation involves either a 5'-->3' exonuclease or is coupled to ongoing translation of the mRNA.
Exon 2-mediated c-myc mRNA decay in vivo is independent of its translation
The results show that the translation of c-myc exon 2 is not required for regulated expression of the transgene in the different situations analyzed, and therefore they indicate that the mRNA destabilizing function of exon 1 is independent of translation by ribosomes, which suggests the existence of tissue-specific mechanisms that control c- myc translatability in vivo.
Rapid mRNA degradation mediated by the c-fos 3' AU-rich element and that mediated by the granulocyte-macrophage colony-stimulating factor 3' AU-rich element occur through similar polysome-associated mechanisms.
Observations demonstrate that the c-fos and granulocyte-macrophage colony-stimulating factor ARE subsets mediate selective mRNA degradation through similar polysome-associated mechanisms coupled with ongoing translation.


Intracellular trafficking of proteins
The role of the endoplasmic reticulum in nascent chain translocation: a perspective from the study of fusion proteins V. SUBRAMANI and C. GOLDSTEIN are highlighted.