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An mTORC1-Mdm2-Drosha axis for miRNA biogenesis in response to glucose- and amino acid-deprivation.

Abstract：

:mTOR senses nutrient and energy status to regulate cell survival and metabolism in response to environmental changes. Surprisingly, targeted mutation of Tsc1, a negative regulator of mTORC1, caused a broad reduction in miRNAs due to Drosha degradation. Conversely, targeted mutation of Raptor, an essential component of mTORC1, increased miRNA biogenesis. mTOR activation increased expression of Mdm2, which is hereby identified as the necessary and sufficient ubiquitin E3 ligase for Drosha. Drosha was induced by nutrient and energy deprivation and conferred resistance to glucose deprivation. Using a high-throughput screen of a miRNA library, we identified four miRNAs that were necessary and sufficient to protect cells against glucose-deprivation-induced apoptosis. These miRNA was regulated by glucose through the mTORC1-MDM2-DROSHA axis. Taken together, our data reveal an mTOR-Mdm2-Drosha pathway in mammalian cells that broadly regulates miRNA biogenesis as a response to alteration in cellular environment.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Ye P,Liu Y,Chen C,Tang F,Wu Q,Wang X,Liu CG,Liu X,Liu R,Liu Y,Zheng P

doi

10.1016/j.molcel.2014.12.034

subject

Has Abstract

pub_date

2015-02-19 00:00:00

pages

708-720

issue

4

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(14)01012-0

journal_volume

57

pub_type

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