A master regulatory network restoring brain glutamate homeostasis is coordinately activated in stroke

Kobayashi, M.; Anderson, C.; Benakis, C.; Moore, M. J.; Mele, A.; Fak, J. J.; Park, C. Y.; Zhou, P.; Anrather, J.; Iadecola, C.; Darnell, R. B.

doi:10.1101/245928

bioRxiv · 10.1101/245928

A master regulatory network restoring brain glutamate homeostasis is coordinately activated in stroke

Kobayashi, M.·Anderson, C.·Benakis, C.·Moore, M. J.·Mele, A.·Fak, J. J.·Park, C. Y.·Zhou, P.·Anrather, J.·Iadecola, C.·Darnell, R. B.

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Abstract

Post-transcriptional regulation by miRNAs is essential for complex molecular responses to physiological insult and disease. Although many disease-associated miRNAs are known, their global targets and culminating network effects on pathophysiology remain poorly understood. We applied AGO CLIP to systematically elucidate altered miRNA-target interactions in brain following ischemia/reperfusion (I/R) injury. Among 1,190 identified, most prominent was the cumulative loss of target regulation by miR-29 family members. Integration of translational and time-course RNA profiles revealed a dynamic mode of miR-29 target de-regulation, led by acute translational activation and later increase in RNA levels, allowing rapid proteomic changes to take effect. These functional regulatory events rely on canonical and non-canonical miR-29 binding and engage glutamate reuptake signals to control local glutamate levels. These results uncover a miRNA target network that acts acutely to maintain brain homeostasis after ischemic stroke.

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Kobayashi, M., Anderson, C., Benakis, C., Moore, M. J., Mele, A., Fak, J. J., Park, C. Y., Zhou, P., Anrather, J., Iadecola, C., Darnell, R. B.. 2018-01-10. A master regulatory network restoring brain glutamate homeostasis is coordinately activated in stroke. https://doi.org/10.1101/245928

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