Intrinsically disordered regions of transcription factor encode multiple functions using interwoven sequence grammars (ChEC-seq)
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PROVIDER: PRJNA1001336 | ENA |
REPOSITORIES: ENA
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Project description:Intrinsically disordered regions (IDRs) are abundant within eukaryotic proteins, but their sequence-function relationship remains poorly understood. IDRs of transcription factors (TFs) can direct promoter selection and recruit coactivators, as exemplified by the budding-yeast TF- Msn2. To examine how low-complexity IDRs encode multiple functions, we compared genomic binding preferences, gene induction, and coactivator recruitment amongst a large set of designed Mns2-IDR mutants. We show that multiple regions across the >500AA IDR contribute to both functions. Yet, transcription activity was readily disrupted by variants having no consequences on Msn2 binding. Our data attribute this differential sensitivity to the integration of relaxed, composition-based code directing binding preferences with a more stringent, motif-based code controlling the recruitment of coactivators and transcription activity. Interwoven sequence grammar may present a general paradigm through which low-complexity IDRs encode multiple functions.
2023-11-19 | GSE239882 | GEO
Project description:Intrinsically disordered regions of transcription factor encode multiple functions using interwoven sequence grammars (RNA-Seq)
| PRJNA1001337 | ENA
Project description:Intrinsically disordered regions of the Msn2 transcription factor encode multiple functions using interwoven sequence grammars
| PRJNA1001333 | ENA
Project description:Intrinsically disordered regions (IDRs) are abundant within eukaryotic proteins, but their sequence-function relationship remains poorly understood. IDRs of transcription factors (TFs) can direct promoter selection and recruit coactivators, as exemplified by the budding-yeast TF- Msn2. To examine how low-complexity IDRs encode multiple functions, we compared genomic binding preferences, gene induction, and coactivator recruitment amongst a large set of designed Mns2-IDR mutants. We show that multiple regions across the >500AA IDR contribute to both functions. Yet, transcription activity was readily disrupted by variants having no consequences on Msn2 binding. Our data attribute this differential sensitivity to the integration of relaxed, composition-based code directing binding preferences with a more stringent, motif-based code controlling the recruitment of coactivators and transcription activity. Interwoven sequence grammar may present a general paradigm through which low-complexity IDRs encode multiple functions.
2023-11-19 | GSE239883 | GEO
Project description:Intrinsically disordered regions regulate RhlE RNA helicase functions in bacteria
| PRJNA1065311 | ENA
Project description:BRCA1/BARD1 is a tumor suppressor E3 ubiquitin (Ub) ligase with roles in DNA damage repair and in transcriptional regulation. BRCA1/BARD1 RING domains interact with nucleosomes to facilitate mono-ubiquitylation of distinct residues on the C-terminal tail of histone H2A. These enzymatic domains constitute a small fraction of the heterodimer, raising the possibility of functional chromatin interactions involving other regions such as the BARD1 C-terminal domains that bind nucleosomes containing the DNA damage signal H2A K15-Ub and H4 K20me0, or portions of the expansive intrinsically disordered regions found in both subunits. Herein, we reveal novel interactions that support robust H2A ubiquitylation activity mediated through a high-affinity, intrinsically disordered DNA-binding region of BARD1. These interactions support BRCA1/BARD1 recruitment to chromatin and sites of DNA damage in cells and contribute to their survival. We also reveal distinct BRCA1/BARD1 complexes that depend on the presence of H2A K15-Ub, including a complex where a single BARD1 subunit spans adjacent nucleosome units. Our findings identify an extensive network of multivalent BARD1-nucleosome interactions that serve as a platform for BRCA1/BARD1-associated functions on chromatin.
2023-06-21 | PXD035345 | Pride
Project description:Comparison of the proteins of thermophilic, mesophilic and psychrophilic prokaryotes has revealed a number of features characteristic to proteins adapted to high temperatures, which increase their thermostability. These characteristics include an excess of disulfide bonds, salt bridges, hydrogen bonds, and hydrophobic interactions, and a depletion in intrinsically disordered regions. It is unclear, however, whether such differences can also be observed when comparing proteins that are adapted to temperatures that are more subtly different. When an organism is exposed to high temperatures, a subset of its proteins are overexpressed (heat-induced proteins), whereas others are repressed (heat-repressed proteins). Here, we determine the expression levels of all Arabidopsis thaliana genes at 22 and 37°C, and compare the amino acid compositions and levels of intrinsic disorder of heat-induced and heat-repressed proteins. We show that heat-induced proteins are enriched in electrostatically charged amino acids and depleted in polar amino acids, mirroring thermopile proteins. However, in contrast with thermophile proteins, heat-repressed proteins are enriched in intrinsically disordered regions and depleted in hydrophobic amino acids. These results indicate that temperature adaptation at the level of amino acid composition and intrinsic disorder can be observed not only in proteins of thermophilic organisms, but also in eukaryotic heat-induced proteins; however, the underlying adaptation pathways are similar but not exactly the same.
2019-05-16 | GSE116592 | GEO
Project description:RNA helicases—central enzymes in RNA metabolism— often feature intrinsically disordered regions (IDRs) that enable phase separation and complex interactions with other proteins and/or RNA molecules. IDRs are varied and fast evolving, which makes their function hard to predict. In the bacterial pathogen Pseudomonas aeruginosa, two non-redundant RNA helicases, RhlE1 and RhlE2, share a conserved REC catalytic core but have different C-terminal extensions (CTEs) composed of IDRs of diverse length and amino acid composition. Here, we show how the IDR diversity defines RhlE RNA helicase specificity of function. Both CTEs facilitate RNA binding and phase separation in vitro, leading to the in vivo localization of proteins in clusters within the cytoplasm. However, the CTE of RhlE2 is more efficient in enhancing REC core RNA unwinding, exhibits a greater tendency for phase separation, and interacts with the RNase E endonuclease, a crucial player in mRNA degradation. Swapping CTEs results in chimeric proteins that are biochemically active but functionally distinct as compared to their native counterparts. The RECRhlE1-CTERhlE2 chimera improves cold growth of a rhlE1 mutant, gains interaction with RNase E and affects a subset of both RhlE1 and RhlE2 RNA targets. The RECRhlE2-CTERhlE1 chimera instead hampers bacterial growth at low temperatures in the absence of RhlE1, with its detrimental effect linked to aberrant RNA droplets. By showing that IDRs modulate both protein core activities and subcellular localization, our study defines the impact of IDR diversity on the functional differentiation of RNA helicases.
2024-05-30 | GSE253333 | GEO
Project description:RNA granules are cellular condensates that contain RNAs and proteins. The mechanism that drive the recruitment of many mRNAs to RNA granules are not fully understood. Here we characterize the assembly and transcriptome of the germ (P) granules of C. elegans. We find that mRNAs are recruited into P granules by condensation with the intrinsically-disordered protein MEG-3. MEG-3 binds ~500 mRNAs in C. elegans embryos in a sequence-independent manner that favors mRNAs with low ribosome coverage. Translational stress causes additional mRNAs to localize to P granules and translational activation correlates with P granule exit for two mRNAs coding for germ cell fate regulators. MEG-3/RNA condensates assembled in vitro are gel-like and trap mRNAs in a non-dynamic state. Our observations reveal similarities between P granules and stress granules and identify gelation with intrinsically-disordered proteins as a sequence-independent mechanism to enrich low-translation mRNAs in RNA granules
2019-12-01 | GSE139879 | GEO
Project description:RNA granules are cellular condensates that contain RNAs and proteins. The mechanism that drive the recruitment of many mRNAs to RNA granules are not fully understood. Here we characterize the assembly and transcriptome of the germ (P) granules of C. elegans. We find that mRNAs are recruited into P granules by condensation with the intrinsically-disordered protein MEG-3. MEG-3 binds ~500 mRNAs in C. elegans embryos in a sequence-independent manner that favors mRNAs with low ribosome coverage. Translational stress causes additional mRNAs to localize to P granules and translational activation correlates with P granule exit for two mRNAs coding for germ cell fate regulators. MEG-3/RNA condensates assembled in vitro are gel-like and trap mRNAs in a non-dynamic state. Our observations reveal similarities between P granules and stress granules and identify gelation with intrinsically-disordered proteins as a sequence-independent mechanism to enrich low-translation mRNAs in RNA granules
2019-12-01 | GSE139878 | GEO