DNA supercoiling-mediated G4/R-loop formation tunes transcription by controlling the access of RNA polymerase

被引:1
作者
Hwang, Jihee [1 ,2 ]
Lee, Chun-Ying [1 ,2 ]
Brahmachari, Sumitabha [3 ]
Tripathi, Shubham [4 ,5 ]
Paul, Tapas [1 ,2 ]
Lee, Huijin [6 ]
Craig, Alanna [7 ]
Ha, Taekjip [1 ,2 ,6 ,7 ,8 ,9 ]
Myong, Sua [1 ,2 ,6 ,7 ]
机构
[1] Boston Childrens Hosp, Programs Cellular & Mol Med, Boston, MA 02115 USA
[2] Harvard Med Sch, Boston, MA 02115 USA
[3] Rice Univ, Ctr Theoret Biol Phys, Houston, TX USA
[4] Yale Ctr Syst & Engn Immunol, Yale Sch Med, New Haven, CT USA
[5] Yale Sch Med, Dept Immunobiol, New Haven, CT USA
[6] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21218 USA
[7] Johns Hopkins Univ, Biophys, Baltimore, MD 21218 USA
[8] Johns Hopkins Univ, Program Cellular Mol Dev Biol, Baltimore, MD USA
[9] Johns Hopkins Univ, Howard Hughes Med Inst, Baltimore, MD USA
关键词
INDUCED FLUORESCENCE ENHANCEMENT; G-QUADRUPLEX STRUCTURES; R-LOOP FORMATION; SMALL-MOLECULE; ELONGATION; INITIATION; KINETICS; REVEALS; EXPRESSION; SELECTION;
D O I
10.1038/s41467-025-58479-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
RNA polymerase (RNAP) is a processive motor that modulates DNA supercoiling and reshapes DNA structures. The feedback loop between the DNA topology and transcription remains elusive. Here, we investigate the impact of potential G-quadruplex forming sequences (PQS) on transcription in response to DNA supercoiling. We find that supercoiled DNA increases transcription frequency 10-fold higher than relaxed DNA, which lead to an abrupt formation of G-quadruplex (G4) and R-loop structures. Moreover, the stable R-loop relieves topological strain, facilitated by G4 formation. The cooperative formation of G4/R-loop effectively alters the DNA topology around the promoter and suppresses transcriptional activity by impeding RNAP loading. These findings highlight negative supercoiling as a built-in spring that triggers a transcriptional burst followed by a rapid suppression upon G4/R-loop formation. This study sheds light on the intricate interplay between DNA topology and structural change in transcriptional regulation, with implications for understanding gene expression dynamics.
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页数:14
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