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| Status |
Public on Apr 20, 2024 |
| Title |
Translationally inhibited mRNAs control cell movement as untranslated sequences [Ribo-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
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.
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| Overall design |
Ribosome profiling from whole cell or isolated focal adhesions from HUVECS (human umbilical vein endothelial cells) or HDFs (Human dermal fibroblasts). Ribosomes in active translation were isolated and the ribosome protected fragments were sequenced
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| Contributor(s) |
Boraas L, Hu M, Martino P, Thornton L, Vejnar CE, Zhen G, Zeng L, Cox AL, Giraldez AJ, Su X, Mayr C, Wang S, Nicoli S |
| Citation missing |
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| Submission date |
Nov 03, 2023 |
| Last update date |
Apr 20, 2024 |
| Contact name |
Liana Boraas |
| E-mail(s) |
liana.boraas@yale.edu
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| Phone |
2037376480
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| Organization name |
Yale University
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| Street address |
300 George Street, Room 752: Loria Center
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| City |
New Haven |
| State/province |
CT |
| ZIP/Postal code |
06511 |
| Country |
USA |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE246956 |
Translationally inhibited mRNAs control cell movement as untranslated sequences |
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| Relations |
| BioProject |
PRJNA1035318 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE246955_nicoli_adhesion_rpf2_run3_count_5_transcript_cds_v2.csv.gz |
1.4 Mb |
(ftp)(http) |
CSV |
| GSE246955_nicoli_adhesion_rpf_wc_run1_count_5_transcript_cds_v2.csv.gz |
1.2 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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