Destabilization of DNA and RNA G-quadruplex structures formed by GGA repeat due to N6-methyladenine modification

Destabilization of DNA and RNA G-quadruplex structures formed by GGA repeat due to N6-methyladenine modification
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DOI:
10.1016/j.bbrc.2022.01.123
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发表时间:
2022-02-07
影响因子:
3.1
通讯作者:
Yoshida, Wataru
Yoshida, Wataru
中科院分区:
生物学4区
文献类型:
--
作者:
Iwasaki, Yuka;Ookuro, Yurino;Yoshida, Wataru

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n -6-甲基腺嘌呤(m(6)A)是真核生物RNA中最丰富的RNA修饰。此外,在真核生物和原核生物的基因组DNA中都发现了m(6)A。G-四重体(G4)结构是由G:G:G:G四分体叠加形成的非典型核酸结构。在本研究中,我们评估了m(6)A修饰对GGA重复寡核苷酸、d(GGA)8、d(GGA)(4)和r(GGA)(4)形成的G4结构的影响。d(GGA)(8)形成分子内四元体:heptad:heptad:四元体G4结构,d(GGA)(4)形成二聚分子间四元体:heptad:heptad:四元体G4结构。r(GGA)(4)形成二聚的分子间四聚体:六聚体:六聚体:四聚体G4结构。圆二色熔融分析表明,(1)m(6)A改性破坏了d(GGA)(8)形成的G4结构,(2)m(6)A改性破坏了d(GGA)(4)形成的G4结构,(3)m(6)A改性破坏了r(GGA)4形成的G4结构。m(6)A修饰可能参与控制G(4)结构形成,从而调节生物学功能。(c) 2022爱思唯尔公司版权所有。
N-6-methyladenine (m(6)A) is the most abundant RNA modification in eukaryotic RNA. Further, m(6)A has been identified in the genomic DNA of both eukaryotes and prokaryotes. The G-quadruplex (G4) structure is a non-canonical nucleic acid structure formed by the stacking of G:G:G:G tetrads. In this study, we evaluated the effect of m(6)A modifications on G4 structures formed by GGA repeat oligonucleotides, d(GGA)8, d(GGA)(4), and r(GGA)(4). The d(GGA)(8) forms an intramolecular tetrad:heptad:heptad:tetrad G4 structure, while d(GGA)(4) forms a dimerized intermolecular tetrad:heptad:heptad:tetrad G4 structure. r(GGA)(4) forms a dimerized intermolecular tetrad:hexad:hexad:tetrad G4 structure. Circular dichroism melting analysis demonstrated that (1) m(6)A modifications destabilized the G4 structure formed by d(GGA)(8), (2) m(6)A modification at A3 disrupted the G4 structure formed by d(GGA)(4), and (3) m(6)A modification at A3 destabilized the G4 structure formed by r(GGA)4. m(6)A modifications may be involved in controlling G(4) structure formation to regulate biological functions. (c) 2022 Elsevier Inc. All rights reserved.