Origin & Evolution of Life

RNA Folding Studies Inside Peptide-rich Droplets Reveal Roles Of Modified Nucleosides At The Origin Of Life

By Keith Cowing
Status Report
March 8, 2023
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RNA Folding Studies Inside Peptide-rich Droplets Reveal Roles Of Modified Nucleosides At The Origin Of Life
tRNA structure-seq in droplets identifies conditions for robust native folding of tRNA. A Scheme of DMS-MaP reaction and data analysis to get the DMS mutation rate at each nucleotide. B-E Predicted structures of Yphe in B Condition A (10mers / 1:1 / 0.5), C Condition C (10mers / 1:1 / 10), D Condition D (10mers / 1:2 / 10), and E Condition F (30mers / 1:2 / 10). F Normalized DMS reactivity of nucleotide A58 under each condition. Bars represent the ShapeMapper2 normalized reactivity of three combined replicates and do not have error bars because they were combined before normalization. Structures in B-E were generated with R2easyR (88) and R2R (89). — biorxiv

Compartmentalization of RNA in biopolymer-rich membraneless organelles is now understood to be pervasive and critical for the function of extant biology and has been proposed as a prebiotically-plausible way to accumulate RNA.

However, compartment-RNA interactions that drive encapsulation have the potential to influence RNA structure and function in compartment- and RNA sequence-dependent ways.

Herein, we detail Next-Generation Sequencing (NGS) experiments performed for the first time in membraneless compartments called complex coacervates to characterize the fold of many different transfer RNAs (tRNAs) simultaneously under the potentially denaturing conditions of these compartments.

Strikingly, we find that natural modifications favor the native fold of tRNAs in these compartments. This suggests that covalent RNA modifications could have played a critical role in metabolic processes at the origin of life.

McCauley O. Meyer, Ryota Yamagami, Saehyun Choi, Christine D. Keating, Philip C. Bevilacqua
doi: https://doi.org/10.1101/2023.02.27.530264

Preprint at https://www.biorxiv.org/

Astrobiology, Genomics

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