Cadherin complexes recruit mRNAs and RISC to regulate epithelial cell signaling

Antonis Kourtidis, Brian Necela, Wan Hsin Lin, Ruifeng Lu, Ryan W. Feathers, Yan Asmann, E Aubrey Thompson, Panagiotis Z Anastasiadis

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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/β-catenin, TGF-β, 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.

Original languageEnglish (US)
Pages (from-to)3073-3085
Number of pages13
JournalJournal of Cell Biology
Volume216
Issue number10
DOIs
StatePublished - Oct 1 2017

Fingerprint

RNA-Induced Silencing Complex
Adherens Junctions
Cadherins
Epithelial Cells
Messenger RNA
MicroRNAs
Catenins
Homeostasis
Stem Cells
RNA
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Cadherin complexes recruit mRNAs and RISC to regulate epithelial cell signaling. / Kourtidis, Antonis; Necela, Brian; Lin, Wan Hsin; Lu, Ruifeng; Feathers, Ryan W.; Asmann, Yan; Thompson, E Aubrey; Anastasiadis, Panagiotis Z.

In: Journal of Cell Biology, Vol. 216, No. 10, 01.10.2017, p. 3073-3085.

Research output: Contribution to journalArticle

Kourtidis, Antonis ; Necela, Brian ; Lin, Wan Hsin ; Lu, Ruifeng ; Feathers, Ryan W. ; Asmann, Yan ; Thompson, E Aubrey ; Anastasiadis, Panagiotis Z. / Cadherin complexes recruit mRNAs and RISC to regulate epithelial cell signaling. In: Journal of Cell Biology. 2017 ; Vol. 216, No. 10. pp. 3073-3085.
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