Cadherin complexes recruit mRNAs and RISC to regulate epithelial cell signaling

Area of Science:

• Molecular Biology
• Cell Biology
• RNA Biology

Background:

• Most RNAs show specific subcellular localization, but regulatory mechanisms and functions are not fully understood.
• RNA-induced silencing complex (RISC) plays a key role in post-transcriptional gene regulation.

Purpose of the Study:

• To investigate the mechanisms and functional consequences of subcellular RNA localization.
• To identify the role of cadherin complexes in recruiting RNA silencing machinery and specific RNAs to epithelial adherens junctions.

Main Methods:

• Localization studies of RISC components (Ago2, GW182, PABPC1), messenger RNAs (mRNAs), and microRNAs (miRNAs) at the apical zonula adherens (ZA).
• Investigation of the role of PLEKHA7 in recruiting these components to the ZA.
• Analysis of mRNA and protein expression levels following PLEKHA7 knockdown.

Main Results:

• Cadherin complexes at the ZA recruit RISC components, 522 mRNAs, and 28 mature miRNAs via PLEKHA7.
• Specific mRNAs (MYC, JUN, SOX2) are present and silenced at the ZA by miR-24 and miR-200c.
• PLEKHA7 knockdown disrupts RISC localization, reduces mRNA/miRNA loading to Ago2, and increases MYC, JUN, and SOX2 protein expression.

Conclusions:

• A novel mechanism links epithelial adherens junction integrity to the silencing of specific mRNAs.
• This pathway, involving PLEKHA7 and RISC at the ZA, critically regulates mRNAs involved in epithelial homeostasis.
• The findings provide insights into how subcellular RNA localization contributes to cellular function and tissue integrity.