Concurrent binding to DNA and RNA facilitates the pluripotency reprogramming activity of Sox2
Concurrent binding to DNA and RNA facilitates the pluripotency reprogramming activity of Sox2
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同时结合 DNA 和 RNA 促进 Sox2 的多能性重编程活性
DOI：
10.1093/nar/gkaa067
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发表时间：
2020-04-17
影响因子：
14.9
通讯作者：
Jauch, Ralf
中科院分区：
文献类型：
--
作者：
Hou, Linlin;Wei, Yuanjie;Jauch, Ralf
一些特异性结合双链DNA的转录因子似乎也具有rna结合蛋白的功能。在这里，我们证明转录因子Sox2能够在体外以及小鼠和人类细胞中直接结合RNA。Sox2通过位于DNA结合高迁移率基团（HMG）盒c端60个氨基酸的RNA结合基序（RBM）靶向RNA。Sox2可以同时与RNA和DNA结合形成三元RNA/Sox2/DNA复合物。RBM的缺失不会影响靶基因的选择，但会减轻与多能性相关转录本的结合，改变外显子的使用，并损害体细胞的重编程，使其进入多能状态。我们的研究结果表明，Sox2是一个与RNA相关的多功能因子，同时与同源DNA序列结合，表明它可能在体细胞重编程过程中共同转录调节RNA代谢。
Abstract Some transcription factors that specifically bind double-stranded DNA appear to also function as RNA-binding proteins. Here, we demonstrate that the transcription factor Sox2 is able to directly bind RNA in vitro as well as in mouse and human cells. Sox2 targets RNA via a 60-amino-acid RNA binding motif (RBM) positioned C-terminally of the DNA binding high mobility group (HMG) box. Sox2 can associate with RNA and DNA simultaneously to form ternary RNA/Sox2/DNA complexes. Deletion of the RBM does not affect selection of target genes but mitigates binding to pluripotency related transcripts, switches exon usage and impairs the reprogramming of somatic cells to a pluripotent state. Our findings designate Sox2 as a multi-functional factor that associates with RNA whilst binding to cognate DNA sequences, suggesting that it may co-transcriptionally regulate RNA metabolism during somatic cell reprogramming.