Systematic identification of post-transcriptional regulatory modules

Matvei Khoroshkin, Andrey Buyan, Martin Dodel, Albertas Navickas, Johnny Yu, Fathima Trejo, Anthony Doty, Rithvik Baratam, Shaopu Zhou, Sean B. Lee, Tanvi Joshi, Kristle Garcia, Benedict Choi, Sohit Miglani, Vishvak Subramanyam, Hailey Modi, Christopher Carpenter, Daniel Markett, M. Ryan Corces, Faraz K. Mardakheh (), Ivan V. Kulakovskiy () and Hani Goodarzi ()
Additional contact information
Matvei Khoroshkin: University of California, San Francisco
Andrey Buyan: Russian Academy of Sciences
Martin Dodel: Queen Mary University of London
Albertas Navickas: University of California, San Francisco
Johnny Yu: University of California, San Francisco
Fathima Trejo: University of San Francisco
Anthony Doty: University of San Francisco
Rithvik Baratam: University of California, San Francisco
Shaopu Zhou: University of California, San Francisco
Sean B. Lee: University of California, San Francisco
Tanvi Joshi: University of California, San Francisco
Kristle Garcia: University of California, San Francisco
Benedict Choi: University of California, San Francisco
Sohit Miglani: University of California, San Francisco
Vishvak Subramanyam: University of California, San Francisco
Hailey Modi: Gladstone Institute of Neurological Disease
Christopher Carpenter: University of California, San Francisco
Daniel Markett: University of California, San Francisco
M. Ryan Corces: Gladstone Institute of Neurological Disease
Faraz K. Mardakheh: Queen Mary University of London
Ivan V. Kulakovskiy: Russian Academy of Sciences
Hani Goodarzi: University of California, San Francisco

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract In our cells, a limited number of RNA binding proteins (RBPs) are responsible for all aspects of RNA metabolism across the entire transcriptome. To accomplish this, RBPs form regulatory units that act on specific target regulons. However, the landscape of RBP combinatorial interactions remains poorly explored. Here, we perform a systematic annotation of RBP combinatorial interactions via multimodal data integration. We build a large-scale map of RBP protein neighborhoods by generating in vivo proximity-dependent biotinylation datasets of 50 human RBPs. In parallel, we use CRISPR interference with single-cell readout to capture transcriptomic changes upon RBP knockdowns. By combining these physical and functional interaction readouts, along with the atlas of RBP mRNA targets from eCLIP assays, we generate an integrated map of functional RBP interactions. We then use this map to match RBPs to their context-specific functions and validate the predicted functions biochemically for four RBPs. This study provides a detailed map of RBP interactions and deconvolves them into distinct regulatory modules with annotated functions and target regulons. This multimodal and integrative framework provides a principled approach for studying post-transcriptional regulatory processes and enriches our understanding of their underlying mechanisms.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-52215-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52215-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-52215-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().