Hippo Signaling Regulates Microprocessor and Links Cell-density-dependent MiRNA Biogenesis to Cancer

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2014 Mar 4

PMID 24581491

Citations 213

Authors

Masaki Mori

Robinson Triboulet

Morvarid Mohseni

Karin Schlegelmilch

Kriti Shrestha

Fernando D Camargo

Richard I Gregory

Affiliations

Soon will be listed here.

Abstract

Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers and can have a causative role in tumorigenesis. The mechanisms responsible for this phenomenon remain poorly understood. Here, we show that YAP, the downstream target of the tumor-suppressive Hippo-signaling pathway regulates miRNA biogenesis in a cell-density-dependent manner. At low cell density, nuclear YAP binds and sequesters p72 (DDX17), a regulatory component of the miRNA-processing machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP facilitates p72 association with Microprocessor and binding to a specific sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of constitutively active YAP causes widespread miRNA suppression in cells and tumors and a corresponding posttranscriptional induction of MYC expression. Thus, the Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be responsible for the widespread miRNA repression observed in cancer.

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