Journal
JOURNAL OF CELL BIOLOGY
Volume 216, Issue 10, Pages 3073-3085Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201612125
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Funding
- National Institutes of Health [R01 CA100467, R01 NS069753, P50 CA116201]
- Mayo Clinic Center for Biomedical Discovery award
- Jay and Deanie Stein Career Development Award for Cancer Research at the Mayo Clinic
- Abney Foundation Scholarship
- Hollings Cancer Center
- American Cancer Society Institutional Research Grant
- 26.2 with Donna Foundation
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Cumulative evidence demonstrates that most RNAs exhibit specific subcellular distribution. However, the mechanisms regulating this phenomenon and its functional consequences are still under investigation. Here, we reveal that cadherin complexes at the apical zonula adherens (ZA) of epithelial adherens junctions recruit the core components of the RNA-induced silencing complex (RISC) Ago2, GW182, and PAB PC1, as well as a set of 522 messenger RNAs (mRNAs) and 28 mature microRNAs (miRNAs or miRs), via PLE KHA7. Top canonical pathways represented by these mRNAs include Wnt/beta-catenin, TGF-beta, and stem cell signaling. We specifically demonstrate the presence and silencing of MYC, JUN, and SOX2 mRNAs by miR-24 and miR-200c at the ZA. PLE KHA7 knockdown dissociates RISC from the ZA, decreases loading of the ZA-associated mRNAs and miRNAs to Ago2, and results in a corresponding increase of MYC, JUN, and SOX2 protein expression. The present work reveals a mechanism that directly links junction integrity to the silencing of a set of mRNAs that critically affect epithelial homeostasis.
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