التفاصيل البيبلوغرافية
| العنوان: |
FMRP promotes transcription-coupled homologous recombination via facilitating TET1-mediated m5C RNA modification demethylation. |
| المؤلفون: |
Haibo Yang, Yumin Wang, Yufei Xiang, Yadav, Tribhuwan, Jian Ouyang, Phoon, Laiyee, Xueping Zhu, Yi Shi, Lee Zou, Li Lan |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 3/22/2022, Vol. 119 Issue 12, p1-12, 12p |
| مصطلحات موضوعية: |
RNA modification & restriction, TRANSGENIC organisms, DEMETHYLATION, DOUBLE-strand DNA breaks, DNA repair, MESSENGER RNA, COMMERCIAL products |
| مستخلص: |
RNA modifications regulate a variety of cellular processes including DNA repair. The RNA methyltransferase TRDMT1 generates methyl-5-cytosine (m5C) on messenger RNA (mRNA) at DNA double-strand breaks (DSBs) in transcribed regions, promoting transcription-coupled homologous recombination (HR). Here, we identified that Fragile X mental retardation protein (FMRP) promotes transcription-coupled HR via its interaction with both the m5C writer TRDMT1 and the m5C eraser ten-eleven translocation protein 1 (TET1). TRDMT1, FMRP, and TET1 function in a temporal order at the transcriptionally active sites of DSBs. FMRP displays a higher affinity for DNA:RNA hybrids containing m5C-modified RNA than for hybrids without modification and facilitates demethylation of m5C by TET1 in vitro. Loss of either the chromatin- or RNA-binding domain of FMRP compromises demethylation of damage-induced m5C in cells. Importantly, FMRP is required for R-loop resolving in cells. Due to unresolved R-loop and m5C preventing completion of DSB repair, FMRP depletion or low expression leads to delayed repair of DSBs at transcriptionally active sites and sensitizes cancer cells to radiation in a BRCA-independent manner. Together, our findings present an m5C reader, FMRP, which acts as a coordinator between the m5C writer and eraser to promote mRNA-dependent repair and cell survival in cancer. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
