Systematic identification of post-transcriptional regulatory modules
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 poorl...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| 格式: | Journal article |
| 語言: | English |
| 出版: |
Nature Research
2024
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| _version_ | 1826314537080455168 |
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| author | Khoroshkin, M Buyan, A Dodel, M Navickas, A Yu, J Trejo, F Doty, A Baratam, R Zhou, S Lee, SB Joshi, T Garcia, K Choi, B Miglani, S Subramanyam, V Modi, H Carpenter, C Markett, D Corces, MR Mardakheh, FK Kulakovskiy, IV Goodarzi, H |
| author_facet | Khoroshkin, M Buyan, A Dodel, M Navickas, A Yu, J Trejo, F Doty, A Baratam, R Zhou, S Lee, SB Joshi, T Garcia, K Choi, B Miglani, S Subramanyam, V Modi, H Carpenter, C Markett, D Corces, MR Mardakheh, FK Kulakovskiy, IV Goodarzi, H |
| author_sort | Khoroshkin, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-09-25T04:34:00Z |
| format | Journal article |
| id | oxford-uuid:beb16e3c-c76c-4238-8a93-db48cde5b910 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:34:00Z |
| publishDate | 2024 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:beb16e3c-c76c-4238-8a93-db48cde5b9102024-09-10T20:11:41ZSystematic identification of post-transcriptional regulatory modulesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:beb16e3c-c76c-4238-8a93-db48cde5b910EnglishJisc Publications RouterNature Research2024Khoroshkin, MBuyan, ADodel, MNavickas, AYu, JTrejo, FDoty, ABaratam, RZhou, SLee, SBJoshi, TGarcia, KChoi, BMiglani, SSubramanyam, VModi, HCarpenter, CMarkett, DCorces, MRMardakheh, FKKulakovskiy, IVGoodarzi, HIn 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. |
| spellingShingle | Khoroshkin, M Buyan, A Dodel, M Navickas, A Yu, J Trejo, F Doty, A Baratam, R Zhou, S Lee, SB Joshi, T Garcia, K Choi, B Miglani, S Subramanyam, V Modi, H Carpenter, C Markett, D Corces, MR Mardakheh, FK Kulakovskiy, IV Goodarzi, H Systematic identification of post-transcriptional regulatory modules |
| title | Systematic identification of post-transcriptional regulatory modules |
| title_full | Systematic identification of post-transcriptional regulatory modules |
| title_fullStr | Systematic identification of post-transcriptional regulatory modules |
| title_full_unstemmed | Systematic identification of post-transcriptional regulatory modules |
| title_short | Systematic identification of post-transcriptional regulatory modules |
| title_sort | systematic identification of post transcriptional regulatory modules |
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