| Autor: |
Kilgas, Susan, Syed, Aleem, Toolan-Kerr, Patrick, Swift, Michelle L., Roychoudhury, Shrabasti, Sarkar, Aniruddha, Wilkins, Sarah, Quigley, Mikayla, Poetsch, Anna R., Botuyan, Maria Victoria, Cui, Gaofeng, Mer, Georges, Ule, Jernej, Drané, Pascal, Chowdhury, Dipanjan |
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| Zdroj: |
Nature Communications; 9/30/2024, Vol. 15 Issue 1, p1-19, 19p |
| Abstrakt: |
Tudor Interacting Repair Regulator (TIRR) is an RNA-binding protein (RBP) that interacts directly with 53BP1, restricting its access to DNA double-strand breaks (DSBs) and its association with p53. We utilized iCLIP to identify RNAs that directly bind to TIRR within cells, identifying the long non-coding RNA NEAT1 as the primary RNA partner. The high affinity of TIRR for NEAT1 is due to prevalent G-rich motifs in the short isoform (NEAT1_1) region of NEAT1. This interaction destabilizes the TIRR/53BP1 complex, promoting 53BP1's function. NEAT1_1 is enriched during the G1 phase of the cell cycle, thereby ensuring that TIRR-dependent inhibition of 53BP1's function is cell cycle-dependent. TDP-43, an RBP that is implicated in neurodegenerative diseases, modulates the TIRR/53BP1 complex by promoting the production of the NEAT1 short isoform, NEAT1_1. Together, we infer that NEAT1_1, and factors regulating NEAT1_1, may impact 53BP1-dependent DNA repair processes, with implications for a spectrum of diseases. TIRR interacts directly with 53BP1, restricting its access to DNA double-strand breaks (DSBs) and its association with p53. Here, the authors show that the lncRNA NEAT1, regulated by TDP-43, destabilizes the TIRR/53BP1 complex in G1, promoting 53BP1's function in DSB repair and p53 transactivation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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