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Related Concept Videos

Regulation of Expression at Multiple Steps01:23

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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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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
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Updated: Sep 18, 2025

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

Abhishek Kumar1, Keiichiro Tanaka1, Martin A Schwartz1,2,3

  • 1Yale Cardiovascular Research Center, Department of Internal Medicine (Division of Cardiovascular Medicine), New Haven, United States.

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|June 26, 2025
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Summary

Cellular focal adhesions drive liquid-liquid phase separation (LLPS) structures that limit mRNA translation. This p130Cas-dependent mechanism regulates cell adhesion and behavior, potentially contributing to quiescent states.

Keywords:
Integrincell adhesioncell biologyextracellular matrixliquid-liquid phase separationnonep130Castranslation

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Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Liquid-liquid phase separation (LLPS) is a key cellular organizing principle.
  • Focal adhesions, crucial for cell adhesion, involve proteins like p130Cas and can undergo LLPS.

Purpose of the Study:

  • To investigate the role of p130Cas in forming cytoplasmic structures with LLPS characteristics.
  • To determine if these structures regulate mRNA translation and cell adhesion.

Main Methods:

  • Inducing LLPS-like structures around p130Cas-coated beads.
  • Isolating these structures to analyze their molecular composition.
  • Using photo-inducible systems (Cry2) to trigger condensate formation.
  • Correlating translation inhibition with focal adhesion size and LLPS.

Main Results:

  • p130Cas drives the formation of LLPS structures budding from focal adhesions.
  • These condensates contain focal adhesion proteins, mRNAs, and RNA-binding proteins that inhibit translation.
  • High fibronectin concentrations induce large focal adhesions, inhibit translation, and correlate with LLPS.
  • Photo-induced p130Cas condensates also reduce mRNA translation.

Conclusions:

  • High cell adhesion induces p130Cas-dependent cytoplasmic LLPS, limiting mRNA translation.
  • This mechanism provides a novel way cells regulate gene expression based on adhesion strength.
  • This process may explain the quiescent state observed in highly adhesive myofibroblasts and senescent cells.