If you aren’t a cell biologist, you may have never heard of focal adhesions (FAs): these are complexes at the surface of many animal cells, mediating the attachment of the cell to its environment and the exertion of force via that environment to help the cell move (or not). FAs are still revealing their secrets, but we know that they contain various specialized proteins that exchange signaling through receptors called integrins. FAs also host a specific mRNA, the one that encodes beta-actin; since actin filaments are a major part of FA structure and function, the role of this RNA is thought to be the maintenance of actin proteins on site.
Beyond that one mRNA, no RNA molecules were known to hang out in FAs. That changed very recently, when a paper in Cell Reports revealed that a major component of FAs is a family of ribonucleoproteins built around components known elsewhere in the cell. Here is how the authors put it:
…a comprehensive understanding of the scope and potential roles of mRNA localization to FAs is unknown.
To fill this knowledge gap, we used an unbiased approach to identify mRNAs and RNA-binding proteins (RBPs) enriched at FAs in normal adherent cells. We detected hundreds of mRNAs and the stress granule (SG) RBP G3BP1 enriched at FAs in unstressed cells. These FA-associated mRNAs (FA-mRNAs) share characteristics with SG mRNAs and form ribonucleoprotein (RNP) complexes with G3BP1 both in vitro and in cellulo. Mechanistically, the RNA-binding domain (RBD) and dimerization domain of G3BP1, essential for G3BP1 to form RNPs in SGs, are also required for its localization to FA and regulation of cell migration speed. We propose that G3BP1 RNPs do not influence translation but rather promote the mobility of FA proteins, thereby affecting adhesion size, a key feature in regulating cell speed.
That is some very interesting new cell biology. But also: note the nice progression in the authors’ writing. In a single paragraph they move from the need (knowledge gap) through the approach to meeting the need, to the results with context, ending with a proposal for why it matters.
And one other thing: a co-first author, Liana Boraas, is a JEDI awardee. Congrats to Liana for that honor and especially for the new paper!
G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration
In Cell Reports, 25 February 2025
From the group of Stefania Nicoli at Yale University School of Medicine
Snippet by Stephen Matheson
Image credit: graphical abstract from Boraas et al. cited above (CC BY-NC-ND)