| Title: |
An intrinsically disordered region mediates RNA-binding selectivity and cellular activities of LARP6 |
| Authors: |
Capraro, Federica; Abis, Giancarlo; Incocciati, Alessio; Simpson, Peter J.; Karimzadeh, Mehran; Masino, Laura; Barley, Alexander; Bui, Tam T. T.; Kelly, Geoff; Goodarzi, Hani; Conte, Maria R.; Mardakheh, Faraz K. |
| Source: |
Capraro, F, Abis, G, Incocciati, A, Simpson, P J, Karimzadeh, M, Masino, L, Barley, A, Bui, T T T, Kelly, G, Goodarzi, H, Conte, M R & Mardakheh, F K 2026, 'An intrinsically disordered region mediates RNA-binding selectivity and cellular activities of LARP6', Nature Communications. https://doi.org/10.1038/s41467-026-69789-z |
| Publication Year: |
2026 |
| Collection: |
King's College, London: Research Portal |
| Description: |
Intrinsically disordered regions (IDRs) are prevalent in RNA-binding proteins (RBPs), yet their roles in RNA interactions remain poorly defined. We examined RNA-binding regulation by structured and disordered regions of LARP6, an RBP with a diverse RNA-binding repertoire. Mass spectrometry-based RNA interaction mapping in living cells identified direct LARP6–RNA contacts within the structured La-module and its flanking IDRs. Mutagenesis and individual-nucleotide resolution UV-crosslinking and immunoprecipitation (iCLIP) revealed the La-module, but not the IDRs, as essential for LARP6 RNA binding. Deletion of the N-terminal IDR broadened LARP6 RNA footprints, uncovering a role in RNA-binding selectivity. This is achieved through a composite mechanism of restricting the conformational flexibility of the adjacent La-module, forming auxiliary contacts with the RNA, and modulating RNA access for binding. The IDR-mediated RNA-binding selectivity is critical for LARP6-mediated promotion of cancer cell viability and invasion. Our findings uncover a previously unrecognised critical function for IDRs in promoting selective RBP–RNA recognition, by affecting the binding specificity of their adjacent structured domains. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pissn/2041-1723; info:eu-repo/semantics/altIdentifier/eissn/2041-1723 |
| DOI: |
10.1038/s41467-026-69789-z |
| Availability: |
https://kclpure.kcl.ac.uk/portal/en/publications/d39a79bc-6838-4ad8-957b-8226e79f963b; https://doi.org/10.1038/s41467-026-69789-z; https://kclpure.kcl.ac.uk/ws/files/365889125/An_intrinsically_disordered_region_mediates_RNA-binding_selectivity_and_cellular_activities_of_LARP6_Version_of_Record.pdf; https://www.nature.com/articles/s41467-026-69789-z |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.15F458FB |
| Database: |
BASE |