Alternative polyadenylation confers PtenmRNAs stability and resistance to microRNAs
| Autor: | Thomas F. Duchaine, Carine Lussier, Hsin-Wei Tseng, Caroline Thivierge, Simon-Pierre Gravel, Vinay K. Mayya |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Gene isoform Untranslated region Polyadenylation RNA Stability Mice 03 medical and health sciences microRNA RNA Isoforms RNA and RNA-protein complexes Genetics Animals Homeostasis Gene silencing PTEN Tensin RNA Messenger 3' Untranslated Regions Messenger RNA biology PTEN Phosphohydrolase RNA-Binding Proteins Cell biology MicroRNAs 030104 developmental biology NIH 3T3 Cells biology.protein |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Fine regulation of the phosphatase and tensin homologue (PTEN) phosphatase dosage is critical for homeostasis and tumour suppression. The 3′-untranslated region (3′-UTR) of Pten mRNA was extensively linked to post-transcriptional regulation by microRNAs (miRNAs). In spite of this critical regulatory role, alternative 3′-UTRs of Pten have not been systematically characterized. Here, we reveal an important diversity of Pten mRNA isoforms generated by alternative polyadenylation sites. Several 3′-UTRs are co-expressed and their relative expression is dynamically regulated. In spite of encoding multiple validated miRNA-binding sites, longer isoforms are largely refractory to miRNA-mediated silencing, are more stable and contribute to the bulk of PTEN protein and signalling functions. Taken together, our results warrant a mechanistic re-interpretation of the post-transcriptional mechanisms involving Pten mRNAs and raise concerns on how miRNA-binding sites are being validated. |
| Databáze: | OpenAIRE |
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