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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 10, 2024 |
| Title |
IGF2BP1 phosphorylation regulates ribonucleoprotein condensate formation by impairing low-affinity protein and RNA interactions (RNA-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The insulin-like growth factor 2 mRNA binding protein (IGF2BP1) is a conserved RNA-binding protein that regulates RNA stability, localization, and translation. IGF2BP1 is part of various ribonucleoprotein (RNP) condensates. However, the mechanism that regulates its assembly into condensates remains unknown. Here we found, using proteomics, that IGF2BP1 phosphorylation at S181 in a disordered linker is regulated in a stress-dependent manner. Phosphomimetic mutations in two disordered linkers, S181E and Y396E, modulated RNP condensate formation by IGF2BP1 without impacting its binding affinity for RNA. Intriguingly, the S181E mutant, which lies in linker 1, impaired IGF2BP1 condensate formation in vitro and in cells, whereas a Y396E mutant in the second linker increased condensate size and dynamics. Structural approaches showed that the first linker binds RNAs nonspecifically through its RGG/RG motif, an interaction weakened in the S181E mutant. Notably, linker 2 interacts with IGF2BP1’s folded domains and these interactions were partially impaired in the Y396E mutant. Our data reveal how phosphorylation modulates low affinity interaction networks in disordered linkers to regulate RNP condensate formation.
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| Overall design |
RNA-Seq of HCT116 cells expressing mCherry-IGF2BP1 WT, S181E, Y396E and RQ (R167Q, R168Q, R174Q, R178Q) mutants and RNA immunoprecipitation sequencing (RIP-Seq) of mCherry-IGF2BP1 WT, S181E, Y396E and RQ mutants in control and arsenate stress conditions
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| Contributor(s) |
Hornegger H, Anisimova AS, Muratovic A, Burgeois B, Spinetti E, Covino R, Madl T, Karagöz GE |
| Citation(s) |
39426983 |
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| Submission date |
Jul 23, 2024 |
| Last update date |
Oct 21, 2024 |
| Contact name |
Aleksandra S Anisimova |
| E-mail(s) |
aleksandra.anisimova@univie.ac.at, alessandrick@gmail.com
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| Organization name |
Max Perutz Labs, Vienna BioCenter, University of Vienna, Medical University of Vienna
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| Lab |
Karagöz Lab
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| Street address |
Dr. Bohr Gasse 9
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| City |
Vienna |
| ZIP/Postal code |
1030 |
| Country |
Austria |
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| Platforms (1) |
| GPL34281 |
Illumina NovaSeq X (Homo sapiens) |
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| Samples (26)
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| GSM8413919 |
mCherry-IGF2BP1 WT, control, rep1, RNA |
| GSM8413920 |
mCherry-IGF2BP1 RQ, control, rep1, RNA |
| GSM8413921 |
mCherry-IGF2BP1 S181E, control, rep1, RNA |
| GSM8413922 |
mCherry-IGF2BP1 Y396E, control, rep1, RNA |
| GSM8413923 |
mCherry-IGF2BP1 WT, arsenite, rep1, RNA |
| GSM8413924 |
mCherry-IGF2BP1 RQ, arsenite, rep1, RNA |
| GSM8413925 |
mCherry-IGF2BP1 S181E, arsenite, rep1, RNA |
| GSM8413926 |
mCherry-IGF2BP1 Y396E, arsenite, rep1, RNA |
| GSM8413927 |
mCherry-IGF2BP1 WT, control, rep2, RNA |
| GSM8413928 |
mCherry-IGF2BP1 RQ, control, rep2, RNA |
| GSM8413929 |
mCherry-IGF2BP1 S181E, control, rep2, RNA |
| GSM8413930 |
mCherry-IGF2BP1 Y396E, control, rep2, RNA |
| GSM8413931 |
mCherry-IGF2BP1 WT, arsenite, rep2, RNA |
| GSM8413932 |
mCherry-IGF2BP1 RQ, arsenite, rep2, RNA |
| GSM8413933 |
mCherry-IGF2BP1 S181E, arsenite, rep2, RNA |
| GSM8413934 |
mCherry-IGF2BP1 Y396E, arsenite, rep2, RNA |
| GSM8413935 |
mCherry-IGF2BP1 WT, control, rep3, RNA |
| GSM8413936 |
mCherry-IGF2BP1 RQ, control, rep3, RNA |
| GSM8413937 |
mCherry-IGF2BP1 S181E, control, rep3, RNA |
| GSM8413938 |
mCherry-IGF2BP1 Y396E, control, rep3, RNA |
| GSM8413939 |
mCherry-IGF2BP1 WT, arsenite, rep3, RNA |
| GSM8413940 |
mCherry-IGF2BP1 RQ, arsenite, rep3, RNA |
| GSM8413941 |
mCherry-IGF2BP1 S181E, arsenite, rep3, RNA |
| GSM8413942 |
mCherry-IGF2BP1 Y396E, arsenite, rep3, RNA |
| GSM8413943 |
HCT116, control, rep1, RNA |
| GSM8413944 |
HCT116, arsenite, rep1, RNA |
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| This SubSeries is part of SuperSeries: |
| GSE272875 |
IGF2BP1 phosphorylation regulates ribonucleoprotein condensate formation by impairing low-affinity protein and RNA interactions |
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| Relations |
| BioProject |
PRJNA1139158 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE272874_RAW.tar |
98.9 Mb |
(http)(custom) |
TAR (of TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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