tRNA modifications as molecular fossils of a protocellular translation system

Chan, Chun-Yin (2025): tRNA modifications as molecular fossils of a protocellular translation system. Dissertation, LMU München: Fakultät für Biologie

Abstract

Centuries of debate on the topics of the origin of life on Earth resulted in the current viewpoint that small organic molecules formed by cosmic or atmospheric phenomena would slowly accumulate and react under prebiotic conditions on the early Earth to form essential precursors that are basic building blocks of primitive biopolymers. Short biopolymers resulting from the random chemical oligomerization of these building blocks could then be selected by their inhabiting environments, and those with the fittest physicochemical properties to accumulate and enrich would polymerize to acquire higher complexity in structures and functions, a process now regarded as ‘chemical evolution’. Among the three component biopolymers of life, namely DNA, RNA and peptides, RNA possesses the capabilities to transfer genetic information by base pairing and perform a wide range of catalytic activities, when folded into ribozymes. Hence, the ‘RNA world’ theory indicates a key period of the chemical evolution in which RNA molecules served as a key hereditary molecule and evolved rapidly to catalyze rudimentary biochemical reactions that progressively shaped the modern biochemistry. However, the RNA world model faces several unanswered questions and one of those being the origin of translation, a process where RNAs are decoded to form peptides and evolved beyond the RNA world. Translation is characterized by two features - a template-directed peptide synthesis and(in) a defined genetic code dictionary. Attempting to address the mystery of the origin of translation, we looked into non-canonical nucleotides that are today found in the tRNAs and rRNAs of the translation machinery, which are highly conservative among all lifeforms on Earth and are considered as ‘molecular fossils’. Since many of them were found to form parallelly with the canonical nucleic acid molecules in various prebiotic reaction pathways, they were likely to be incorporated into early RNA oligonucleotides and served important roles in the early functionalization and survival of RNA. In this thesis, we designed the chemical synthesis of these modified RNAs and investigated their physicochemical properties. We built a model in which these modifications could perform template-directed peptide synthesis and acquire elementary chemoselectivity by liposome interactions.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
• Fakultäten: Fakultät für Biologie
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 11. Februar 2025
• 1. Bericht­erstatter:in: Carell, Thomas