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Translationally inhibited mRNAs control cell movement as untranslated sequences [RNA-seq]

ABSTRACT: Translation of localized mRNAs serves to regulate specific sites of protein synthesis and its functional activity, whereas translationally inhibited and untranslated mRNAs are compartmentalized for degradation or storage, with no recognized functional role. Here, however, we unexpectedly discover a group of functional, untranslated mRNA sequences that localize to integrin focal adhesions (FAs), dynamic multiprotein assemblies that govern cell movement. We show that specific mRNA sequences associate with native or mature FA functional states via messenger ribonucleoprotein (mRNP) complexes with the RNA and FA binding protein G3BP1, functioning to regulate cell migration. Mechanistically, the dimerizing propensity of the mRNA in G3BP1 mRNPs directly regulates FA protein function. Self-dimerizing mRNA sequences form large branched G3BP1 mRNPs, reducing FA protein turnover and extending adhesion lifetimes, inhibiting cell migration. In contrast, low self-dimerization promotes small more spheric G3BP1 mRNPs, facilitating FA complex dissolution and enhancing cell migration behaviors. Our findings define a previously unknown role for cytoplasmic mRNAs, challenging the notion that mRNAs are solely coding molecules and shedding light on their regulatory functions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE246499 | GEO | 2024/04/20

REPOSITORIES: GEO

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