Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Kinetic Explanations for the Sequence Biases Observed in the Nonenzymatic Copying of RNA Templates The identification of nonenzymatic pathways for nucleic acid replication is a key challenge in understanding the origin of life. We have previously shown that nonenzymatic RNA primer extension using 2-aminoimidazole (2AI) activated nucleotides occurs primarily through an imidazolium-bridged dinucleotide intermediate. The reactive nature and preorganized structure of the intermediate increase the efficiency of primer extension but remain insufficient to drive extensive copying of RNA templates containing all four canonical nucleotides. To understand the factors that limit RNA copying, we synthesized all ten 2AI-bridged dinucleotide intermediates and measured the kinetics of primer extension in a model. The affinities of the ten dinucleotides for the primer/template/helper complexes vary by over 7,000-fold, consistent with nearest neighbor energetic predictions. Surprisingly, the reaction rates at saturating intermediate concentrations still vary by over 15-fold, with the most weakly binding dinucleotides exhibiting a lower maximal reaction rate. Certain noncanonical nucleotides can decrease sequence dependent differences in affinity and primer extension rate, while monomers bridged to short oligonucleotides exhibit enhanced binding and reaction rates. We suggest that more uniform binding and reactivity of imidazolium-bridged intermediates may lead to the ability to copy arbitrary template sequences under prebiotically plausible conditions.
24
The categories of this paper are: cancer
13
The categories of this paper are: animal
0
The categories of this paper are: genetics
29
The categories of this paper are: education
1
The categories of this paper are: bioinformatics
22
The categories of this paper are: physiology
10
The categories of this paper are: and
28
The categories of this paper are: communication
9
The categories of this paper are: synthetic
27
The categories of this paper are: pathology
12
The categories of this paper are: behavior
32
The categories of this paper are: zoology
6
The categories of this paper are: plant
18
The categories of this paper are: systems
20
The categories of this paper are: pharmacology
3
The categories of this paper are: evolutionary