Dual DNA/RNA-binding factor regulates dynamics of hnRNP splicing condensates

Ray, Mukulika; Zaborowsky, Julia; Mahableshwarkar, Pranav; Vaidyanathan, Smriti; Shum, Jasmine; Viswanathan, Renjith; Huang, Annie; Wang, Szu-Huan; Johnson, Victoria; Wake, Noah; Conard, Ashley M.; Conicella, Alexander E.; Puterbaugh, Ryan; Fawzi, Nicolas L.; Larschan, Erica

doi:10.1101/2024.01.11.575216

Cited by 2 publications

(1 citation statement)

References 52 publications

(92 reference statements)

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“…One can also do individual chromosome-wide binding analysis with BindCompare. We compared the binding of the male X-chromosome enriched Drosophila transcription factor CLAMP at genomic locations on DNA (# GSE220053) with its RNA targets (# GSE205987) in male cells (Ilik et al 2013; Soruco et al 2013; Ray et al 2024). Using BindCompare for individual chromosome-wise overlap profiles, we show that CLAMP-DNA peaks overlapping with RNA peaks are more frequently distributed on X-chromosomes than autosomes ( Supp.…”

Section: Resultsmentioning

confidence: 99%

BindCompare: A Novel Integrated protein-nucleic Acid Binding Analysis Platform

Mahableshwarkar,

Shum,

Ray

et al. 2024

Preprint

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Advanced genomic technologies have generated thousands of Protein-Nucleic acid binding datasets that have the potential to identify testable gene regulatory network (GRNs) models governed by combinatorial associations between factors. Transcription factors (TFs) and RNA binding proteins (RBPs) are nucleic-acid binding proteins regulating gene expression and are key drivers of GRN function. However, the combinatorial mechanisms by which the interactions between specific TFs and RBPs regulate gene expression remain largely unknown. To identify possible combinations of TFs and RBPs that may function together, developing a tool that compares and contrasts the interactions of multiple TFs and RBPs with nucleic acids to identify their common and unique targets is necessary. Therefore, we introduce BindCompare, a user-friendly tool that can be run locally to predict new combinatorial relationships between TFs and RBPs. BindCompare can analyze data from any organism with known annotated genome information and outputs files with detailed genomic locations and gene information for targets for downstream analysis. Overall, Bindcompare is a new tool that identifies TFs and RBPs that co-bind to the same DNA and/or RNA loci, generating testable hypotheses about their combinatorial regulation of target genes.BindCompare is an open-source package that is available on the Python Packaging Index (PyPI,https://pypi.org/project/bindcompare/) with the source code available on GitHub (https://github.com/pranavmahabs/bindcompare). Complete documentation for the package can be found at both of these links.

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Section: Resultsmentioning

confidence: 99%

BindCompare: A Novel Integrated protein-nucleic Acid Binding Analysis Platform

Mahableshwarkar,

Shum,

Ray

et al. 2024

Preprint

Self Cite

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Arid5a uses disordered extensions of its core ARID domain for distinct DNA- and RNA-recognition and gene regulation

von Ehr,

Oberstrass,

Yazgan

et al. 2024

Preprint

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AT-rich interacting domain (ARID)-containing proteins, Arids, are a heterogeneous DNA-binding protein family involved in transcription regulation and chromatin processing. For the member Arid5a, no exact DNA-binding preference has been experimentally defined so far. Additionally, the protein binds to mRNA motifs for transcript stabilization, supposedly through the DNA-binding ARID domain. To date, however, no unbiased RNA motif definition and clear dissection of nucleic acid-binding through the ARID domain have been undertaken. Using NMR-centered biochemistry, we here define the Arid5a DNA preference. Further, high-throughput in vitro binding (RBNS) reveals a consensus RNA-binding motif engaged by the core ARID domain. Finally, transcriptome-wide binding (iCLIP2) reveals that Arid5a has a weak preference for (A)U-rich regions in pre-mRNA transcripts of factors related to RNA processing. We find that the intrinsically disordered regions (IDR) flanking the ARID domain modulate the specificity and affinity of DNA-binding, while they appear crucial for RNA interactions. Ultimately, our data suggest that Arid5a uses its extended ARID domain for bi-functional gene regulation and that the involvement of IDR extensions is a more general feature of Arids in interacting with different nucleic acids at the chromatin-mRNA interface.

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Dual DNA/RNA-binding factor regulates dynamics of hnRNP splicing condensates

Cited by 2 publications

References 52 publications

BindCompare: A Novel Integrated protein-nucleic Acid Binding Analysis Platform

BindCompare: A Novel Integrated protein-nucleic Acid Binding Analysis Platform

Arid5a uses disordered extensions of its core ARID domain for distinct DNA- and RNA-recognition and gene regulation

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