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Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...

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Related Experiment Video

Updated: Jul 9, 2025

Quantitative Immunofluorescence to Measure Global Localized Translation

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Published on: August 22, 2017

Focal adhesion-derived liquid-liquid phase separations regulate mRNA translation.

Abhishek Kumar¹, Keiichiro Tanaka¹, Martin A Schwartz^1,2,3

¹Yale Cardiovascular Research Center, Department of Internal Medicine (Division of Cardiovascular Medicine), 300 George St. New Haven CT 06511.

Biorxiv : the Preprint Server for Biology

|December 4, 2023

Summary

Cell adhesion protein p130Cas drives liquid-liquid phase separation (LLPS) condensates that inhibit mRNA translation. This novel mechanism links cell adhesion strength to protein synthesis regulation, impacting cell states like quiescence.

Keywords:

cell adhesion condensate extracellular matrix integrin p130Cas

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Area of Science:

Cell Biology
Biochemistry
Molecular Biology

Background:

Liquid-liquid phase separation (LLPS) is a key cellular organizing principle.
Integrin-mediated focal adhesions and proteins like p130Cas are known to undergo LLPS.
LLPS in focal adhesions influences cell adhesion dynamics and behavior.

Purpose of the Study:

To investigate the role of p130Cas in forming cytoplasmic structures with LLPS characteristics.
To determine if these p130Cas condensates regulate mRNA translation.
To elucidate a novel mechanism linking cell adhesion to translation control.

Main Methods:

Inducing LLPS-like structures around p130Cas-coated beads.
Isolating and analyzing the composition of these condensates.
Utilizing high fibronectin concentrations to induce large focal adhesions.
Employing photo-inducible Cry2 system for condensate induction.
Measuring mRNA translation rates in response to these conditions.

Main Results:

p130Cas drives the formation of LLPS-like structures budding from focal adhesions.
These condensates are enriched with focal adhesion proteins, mRNAs, and RNA-binding proteins, including translation inhibitors.
High fibronectin concentrations induce focal adhesions that inhibit mRNA translation, dependent on p130Cas and correlated with droplet formation.
Photo-induction of p130Cas condensates also reduced translation.

Conclusions:

A novel regulatory mechanism is identified where high cell adhesion limits mRNA translation through p130Cas-dependent cytoplasmic LLPS.
This mechanism may explain the quiescent state observed in strongly adhesive myofibroblasts and senescent cells.
p130Cas-driven LLPS acts as a critical link between cell adhesion and translational control.