p53 and HuR combinatorially control the biphasic dynamics of microRNA-125b in response to genotoxic stress

Binita Goswami (1) , Deepika Ahuja (1) , David Pastré (2) , Partho Sarothi Ray (1)

1 IISER Kolkata - Indian Institute of Science Education and Research Kolbata
2 SABNP - Structure et activité des biomolécules normales et pathologiques

Post-transcriptional regulation of p53, by the microRNA miR-125b and the RNA-binding protein HuR, controls p53 expression under genotoxic stress. p53 mRNA translation is repressed by miR-125b, tightly regulating its basal level of expression. The repression is relieved upon DNA damage by a decrease in miR-125b level, contributing to pulsatile expression of p53. The pulse of p53, as also of HuR, in response to UV irradiation coincides with a time-dependent biphasic change in miR-125b level. We show that the cause for the decrease in miR-125b level immediately post DNA-damage is enhanced exosomal export mediated by HuR. The subsequent increase in miR-125b level is due to p53-mediated transcriptional upregulation and enhanced processing, demonstrating miR-125b as a transcriptional and processing target of p53. p53 activates the transcription of primary miR-125b RNA from a cryptic promoter in response to UV irradiation. Together, these regulatory processes constitute reciprocal feedback loops that determine the biphasic change in miR-125b level, ultimately contributing to the fine-tuned temporal regulation of p53 expression in response to genotoxic stress.

Domaines: Sciences du Vivant [q-bio]

Binita Goswami, Deepika Ahuja, David Pastré, Partho Sarothi Ray. p53 and HuR combinatorially control the biphasic dynamics of microRNA-125b in response to genotoxic stress. Communications Biology, 2023, 6 (1), pp.110. ⟨10.1038/s42003-023-04507-9⟩. ⟨hal-04231533⟩