Journal
NUCLEIC ACIDS RESEARCH
Volume 46, Issue 19, Pages 10340-10352Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gky666
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Funding
- Cancer Research Society (CRS)
- Canadian Institute of Health Research (CIHR) [MOP-123352]
- Fonds de la Rercherche en Sante du Quebec
- Chercheur-Boursier Senior salary award
- Susan G. Komens fellowship
- CIHR [MOP-123352]
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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.
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