Department of Biochemistry, Molecular Cancer Research Center, School of Medicine, Sun Yat-Sen University, Guangzhou/Shenzhen, China.
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences and Guangzhou Medical University, Guangzhou 511436, China.
Nucleic Acids Res. 2020 Apr 17;48(7):3869-3887. doi: 10.1093/nar/gkaa067.
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.
一些专门结合双链 DNA 的转录因子似乎也能作为 RNA 结合蛋白发挥作用。在这里，我们证明转录因子 Sox2 能够在体外以及在小鼠和人类细胞中直接结合 RNA。Sox2 通过位于 DNA 结合高迁移率族（HMG）盒 C 末端的 60 个氨基酸 RNA 结合基序（RBM）靶向 RNA。Sox2 可以与 RNA 和 DNA 同时结合形成三元 RNA/Sox2/DNA 复合物。删除 RBM 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重编程为多能状态。我们的发现将 Sox2 指定为一种多功能因子，它与 RNA 结合的同时也与同源 DNA 序列结合，这表明它可能在体细胞重编程过程中通过共转录调节 RNA 代谢。
