scholarly journals A quantitative model predicts how m6A reshapes the kinetic landscape of nucleic acid hybridization and conformational transitions

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bei Liu ◽  
Honglue Shi ◽  
Atul Rangadurai ◽  
Felix Nussbaumer ◽  
Chia-Chieh Chu ◽  
...  

ABSTRACTN6-methyladenosine (m6A) is a post-transcriptional modification that controls gene expression by recruiting proteins to RNA sites. The modification also slows biochemical processes through mechanisms that are not understood. Using temperature-dependent (20°C–65°C) NMR relaxation dispersion, we show that m6A pairs with uridine with the methylamino group in the anti conformation to form a Watson-Crick base pair that transiently exchanges on the millisecond timescale with a singly hydrogen-bonded low-populated (1%) mismatch-like conformation in which the methylamino group is syn. This ability to rapidly interchange between Watson-Crick or mismatch-like forms, combined with different syn:anti isomer preferences when paired (~1:100) versus unpaired (~10:1), explains how m6A robustly slows duplex annealing without affecting melting at elevated temperatures via two pathways in which isomerization occurs before or after duplex annealing. Our model quantitatively predicts how m6A reshapes the kinetic landscape of nucleic acid hybridization and conformational transitions, and provides an explanation for why the modification robustly slows diverse cellular processes.

Author(s):  
Bei Liu ◽  
Honglue Shi ◽  
Atul Rangadurai ◽  
Felix Nussbaumer ◽  
Chia-Chieh Chu ◽  
...  

ABSTRACTN6-methyladenosine (m6A) is a post-transcriptional modification that controls gene expression by recruiting proteins to RNA sites. The modification also slows biochemical processes through mechanisms that are not understood. Using NMR relaxation dispersion, we show that m6A pairs with uridine with the methylamino group in the anti conformation to form a Watson-Crick base pair that transiently exchanges on the millisecond timescale with a singly hydrogen-bonded low-populated (1%) mismatch-like conformation in which the methylamino group is syn. This ability to rapidly interchange between Watson-Crick or mismatch-like forms, combined with different syn:anti isomer preferences when paired (~1:100) versus unpaired (~10:1), explains how m6A robustly slows duplex annealing without affecting melting via two pathways in which isomerization occurs before or after duplex annealing. Our model quantitatively predicts how m6A reshapes the kinetic landscape of nucleic acid hybridization and conformational transitions, and provides an explanation for why the modification robustly slows diverse cellular processes.


Langmuir ◽  
2008 ◽  
Vol 24 (21) ◽  
pp. 12483-12488 ◽  
Author(s):  
Wui Siew Tan ◽  
Christina L. Lewis ◽  
Nicholas E. Horelik ◽  
Daniel C. Pregibon ◽  
Patrick S. Doyle ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anthony C. Yu ◽  
Huada Lian ◽  
Xian Kong ◽  
Hector Lopez Hernandez ◽  
Jian Qin ◽  
...  

AbstractPhysical networks typically employ enthalpy-dominated crosslinking interactions that become more dynamic at elevated temperatures, leading to network softening. Moreover, standard mathematical frameworks such as time-temperature superposition assume network softening and faster dynamics at elevated temperatures. Yet, deriving a mathematical framework connecting the crosslinking thermodynamics to the temperature-dependent viscoelasticity of physical networks suggests the possibility for entropy-driven crosslinking interactions to provide alternative temperature dependencies. This framework illustrates that temperature negligibly affects crosslink density in reported systems, but drastically influences crosslink dynamics. While the dissociation rate of enthalpy-driven crosslinks is accelerated at elevated temperatures, the dissociation rate of entropy-driven crosslinks is negligibly affected or even slowed under these conditions. Here we report an entropy-driven physical network based on polymer-nanoparticle interactions that exhibits mechanical properties that are invariant with temperature. These studies provide a foundation for designing and characterizing entropy-driven physical crosslinking motifs and demonstrate how these physical networks access thermal properties that are not observed in current physical networks.


Plant Disease ◽  
1998 ◽  
Vol 82 (4) ◽  
pp. 419-422 ◽  
Author(s):  
A. G. Gillaspie ◽  
M. R. Hajimorad ◽  
S. A. Ghabrial

A new seedborne strain of cucumber mosaic cucumovirus (CMV) that induces severe symptoms on many cowpea genotypes was detected in Georgia in 1994. This strain, designated CMV-Csb, is asymptomatic on tobacco, but it produces more severe cowpea stunt symptoms when present in combination with blackeye cowpea mosaic potyvirus than do the more prevalent CMV isolates. The new strain is seedborne in cowpea (1.5 to 37%), has no associated satellite RNA, and is classified as a member of subgroup I of CMV strains based on nucleic acid hybridization assays.


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