TY - JOUR
T1 - Cadherin complexes recruit mRNAs and RISC to regulate epithelial cell signaling
AU - Kourtidis, Antonis
AU - Necela, Brian
AU - Lin, Wan Hsin
AU - Lu, Ruifeng
AU - Feathers, Ryan W.
AU - Asmann, Yan W.
AU - Aubrey Thompson, E.
AU - Anastasiadis, Panos Z.
N1 - Publisher Copyright:
© 2017 Kourtidis et al.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.201612125
DO - 10.1083/jcb.201612125
M3 - Article
C2 - 28877994
AN - SCOPUS:85030259428
SN - 0021-9525
VL - 216
SP - 3073
EP - 3085
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 10
ER -