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• W2912245607 abstract "Transposable elements (TEs) comprise a large proportion of long non-coding RNAs (lncRNAs). Here, we employed CRISPR to delete a short interspersed nuclear element (SINE) in Malat1, a cancer-associated lncRNA, to investigate its significance in cellular physiology. We show that Malat1 with a SINE deletion forms diffuse nuclear speckles and is frequently translocated to the cytoplasm. SINE-deleted cells exhibit an activated unfolded protein response and PKR and markedly increased DNA damage and apoptosis caused by dysregulation of TDP-43 localization and formation of cytotoxic inclusions. TDP-43 binds stronger to Malat1 without the SINE and is likely 'hijacked' by cytoplasmic Malat1 to the cytoplasm, resulting in the depletion of nuclear TDP-43 and redistribution of TDP-43 binding to repetitive element transcripts and mRNAs encoding mitotic and nuclear-cytoplasmic regulators. The SINE promotes Malat1 nuclear retention by facilitating Malat1 binding to HNRNPK, a protein that drives RNA nuclear retention, potentially through direct interactions of the SINE with KHDRBS1 and TRA2A, which bind to HNRNPK. Losing these RNA-protein interactions due to the SINE deletion likely creates more available TDP-43 binding sites on Malat1 and subsequent TDP-43 aggregation. These results highlight the significance of lncRNA TEs in TDP-43 proteostasis with potential implications in both cancer and neurodegenerative diseases." @default.
• W2912245607 created "2019-02-21" @default.
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• W2912245607 date "2019-12-21" @default.
• W2912245607 modified "2023-10-16" @default.
• W2912245607 title "The SINEB1 element in the long non-coding RNA Malat1 is necessary for TDP-43 proteostasis" @default.
• W2912245607 cites W1697178647 @default.
• W2912245607 cites W1879996757 @default.
• W2912245607 cites W1963522988 @default.
• W2912245607 cites W1966682365 @default.
• W2912245607 cites W1969161156 @default.
• W2912245607 cites W1970090817 @default.
• W2912245607 cites W1972104572 @default.
• W2912245607 cites W1972673499 @default.
• W2912245607 cites W1977709885 @default.
• W2912245607 cites W1977943782 @default.
• W2912245607 cites W1992673430 @default.
• W2912245607 cites W2008334829 @default.
• W2912245607 cites W2014677321 @default.
• W2912245607 cites W2024715297 @default.
• W2912245607 cites W2030658020 @default.
• W2912245607 cites W2031646822 @default.
• W2912245607 cites W2040469179 @default.
• W2912245607 cites W2050982262 @default.
• W2912245607 cites W2051282896 @default.
• W2912245607 cites W2058056744 @default.
• W2912245607 cites W2083031173 @default.
• W2912245607 cites W2087528029 @default.
• W2912245607 cites W2092886041 @default.
• W2912245607 cites W2098978914 @default.
• W2912245607 cites W2099540110 @default.
• W2912245607 cites W2101042581 @default.
• W2912245607 cites W2107454957 @default.
• W2912245607 cites W2120772351 @default.
• W2912245607 cites W2122576011 @default.
• W2912245607 cites W2126569879 @default.
• W2912245607 cites W2131640859 @default.
• W2912245607 cites W2131725903 @default.
• W2912245607 cites W2136949432 @default.
• W2912245607 cites W2150757282 @default.
• W2912245607 cites W2154942446 @default.
• W2912245607 cites W2168453644 @default.
• W2912245607 cites W2169092675 @default.
• W2912245607 cites W2191641478 @default.
• W2912245607 cites W2201924392 @default.
• W2912245607 cites W2216341974 @default.
• W2912245607 cites W2307041907 @default.
• W2912245607 cites W2333541540 @default.
• W2912245607 cites W2388201280 @default.
• W2912245607 cites W2419386157 @default.
• W2912245607 cites W2427010553 @default.
• W2912245607 cites W2472573833 @default.
• W2912245607 cites W2509717357 @default.
• W2912245607 cites W2518959324 @default.
• W2912245607 cites W2521797369 @default.
• W2912245607 cites W2605972662 @default.
• W2912245607 cites W2624386673 @default.
• W2912245607 cites W2754846502 @default.
• W2912245607 cites W2756634225 @default.
• W2912245607 cites W2769039165 @default.
• W2912245607 cites W2788747005 @default.
• W2912245607 cites W2789891087 @default.
• W2912245607 cites W2789956212 @default.
• W2912245607 cites W2804494174 @default.
• W2912245607 cites W2805240258 @default.
• W2912245607 cites W2807481171 @default.
• W2912245607 cites W2897570487 @default.
• W2912245607 cites W2938574745 @default.
• W2912245607 cites W2942885970 @default.
• W2912245607 cites W2944708767 @default.
• W2912245607 cites W2951215750 @default.
• W2912245607 cites W4246488417 @default.
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• W2912245607 doi "https://doi.org/10.1093/nar/gkz1176" @default.
• W2912245607 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7049706" @default.

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