ArticleThe Journal of biological chemistry2005
A hairpin-like structure within an AU-rich mRNA-destabilizing element regulates trans-factor binding selectivity and mRNA decay kinetics.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 85 citations in OpenAlex.
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- Detecting and quantifying overparametrization in RNA language models with REDIAL.bioRxiv : the preprint server for biology · 2026Article
- Comparative Analysis of Insect Resistance in TransgenicPlants (Basel, Switzerland) · 2025Article
- Unstructured protein domains stabilize RNA binding and mediate RNA folding by AUF1.The Journal of biological chemistry · 2025Article
- The short conserved region-2 of LARP4 interacts with ribosome-associated RACK1 and promotes translation.Nucleic acids research · 2025Article
- The short conserved region-2 of LARP4 interacts with ribosome-associated RACK1 and promotes translation.bioRxiv : the preprint server for biology · 2024Article
- hnRNPs: roles in neurodevelopment and implication for brain disorders.Frontiers in molecular neuroscience · 2024Review
- Review
- High-throughput techniques enable advances in the roles of DNA and RNA secondary structures in transcriptional and post-transcriptional gene regulation.Genome biology · 2022Review
- The function and regulatory mechanism of RNA-binding proteins in breast cancer and their future clinical treatment prospects.Frontiers in oncology · 2022Review
- PRMT5 Interacting Partners and Substrates in Oligodendrocyte Lineage Cells.Frontiers in cellular neuroscience · 2022Article
- The isolated La-module of LARP1 mediates 3' poly(A) protection and mRNA stabilization, dependent on its intrinsic PAM2 binding to PABPC1.RNA biology · 2021Article
- Structural basis for the recognition of transiently structured AU-rich elements by Roquin.Nucleic acids research · 2020Article
- Effect of Exposure to Seminal Plasma Through Natural Mating in Cattle on Conceptus Length and Gene Expression.Frontiers in cell and developmental biology · 2020Article
- The RGG/RG motif of AUF1 isoform p45 is a key modulator of the protein's RNA chaperone and RNA annealing activities.RNA biology · 2019Article
- Article
- Hsp70's RNA-binding and mRNA-stabilizing activities are independent of its protein chaperone functions.The Journal of biological chemistry · 2017Article
- Impact of RNA structure on ZFP36L2 interaction with luteinizing hormone receptor mRNA.RNA (New York, N.Y.) · 2017Article
- AUF1 regulation of coding and noncoding RNA.Wiley interdisciplinary reviews. RNA · 2017Review
- Post-transcriptional regulation of cytokine and growth factor signaling in cancer.Cytokine & growth factor reviews · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
In mammals, rapid mRNA turnover directed by AU-rich elements (AREs) is mediated by selective association of cellular ARE-binding proteins. These trans-acting factors display overlapping RNA substrate specificities and may act to either stabilize or destabilize targeted transcripts; however, the mechanistic features of AREs that promote preferential binding of one trans-factor over another are not well understood. Here, we describe a hairpin-like structure adopted by the ARE from tumor necrosis factor alpha (TNFalpha) mRNA that modulates its affinity for selected ARE-binding proteins. In particular, association of the mRNA-destabilizing factor p37(AUF1) was strongly inhibited by adoption of the higher order ARE structure, whereas binding of the inducible heat shock protein Hsp70 was less severely compromised. By contrast, association of the mRNA-stabilizing protein HuR was only minimally affected by changes in ARE folding. Consistent with the inverse relationship between p37(AUF1) binding affinity and the stability of ARE folding, mutations that stabilized the ARE hairpin also inhibited its ability to direct rapid mRNA turnover in transfected cells. Finally, phylogenetic analyses and structural modeling indicate that TNFalpha mRNA sequences flanking the ARE are highly conserved and may stabilize the hairpin fold in vivo. Taken together, these data suggest that local higher order structures involving AREs may function as potent regulators of mRNA turnover in mammalian cells by modulating trans-factor binding selectivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.