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. 2019 Dec;29(12):1035-1038.
doi: 10.1038/s41422-019-0235-7. Epub 2019 Oct 12.

m6A promotes R-loop formation to facilitate transcription termination

Xin Yang #  1 , Qian-Lan Liu #  1   2 , Wei Xu #  3 , Yi-Chang Zhang #  1   2 , Ying Yang  1   2   4 , Lin-Fang Ju  1   2 , Jing Chen  1   2 , Yu-Sheng Chen  1   2 , Kuan Li  3 , Jie Ren  5   6   7   8 , Qianwen Sun  9 , Yun-Gui Yang  10   11   12   13
Affiliations

m6A promotes R-loop formation to facilitate transcription termination

Xin Yang et al. Cell Res. 2019 Dec.
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
m6A promotes R-loop formation to facilitate transcription termination. a Dot blot assay and quantitative analysis of R-loops upon METTL3 knockdown. RNase H treatment was performed as the control treatment. Methylene blue staining indicates equal DNA loading. b Quantification of m6A levels demonstrated as bar plots comparing input and DRIPed RNA samples. c Metaplot of R-loop enrichments from m6A+ genes in shCTRL (gray) and shMETTL3 (red) cells. R-loop enrichments in randomized regions are shown as the green (shCTRL) and blue (shMETTL3) lines. d The number of windows with decreased (blue) and increased (purple) R-loop levels in the promoter region, four quarters of the gene body and the terminator region of m6A+ genes. e The ratio of decreased to increased R-loop window numbers in m6A+ genes (orange) and m6A− genes (blue). f, g Box plots showing that R-loop fold changes (shMETTL3 vs. shCTRL) in terminator regions are influenced by their distance to m6A (f) and the strength of m6A modification (g). h, i Cumulative distributions showing changes of readthrough in regions from TES to 2 kb downstream (h TES + 2 kb) and from 2 kb upstream to TES (i TES-2kb) in m6A+ and m6A− genes. j Genomic visualization of ssDRIP-seq and mNET-seq on MYC gene. m6A modification sites are shown by red triangles. k Structure of MYC gene. l pSer2-Pol II ChIP with probes downstream of TES of MYC. m Br-UTP NRO analysis of MYC. n Cartoon for the minigene reporter system. The MYC gene terminator region, which contains m6A sites (red triangles) or mutated sites, was inserted into a dual luciferase reporter vector. o–q Quantification of m6A (o), R-loops (p) and readthrough products (q) shown as bar plots comparing wild-type and mutant reporters. r, s Quantification of R-loops (r) and readthrough products (s) of the wild-type and mutant reporters upon METTL3 depletion. t Working model showing that METTL3 installs m6A methylation to nascent RNAs and promotes R-loop formation in the terminator regions to facilitate transcription termination. The error bars of a, l, m, and o–s indicate ± SEM (n = 3). P values of a–c, l, m, and o–s were calculated using Student’s t-test. P values of f–i determined by Mann–Whitney U test are shown
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