Exobiology and Evolutionary Biology

Molecular and genetic investigations of RNA stability in hyperthermophilic Archaea

PI: Dirk Iwata-Reuyl

RNA occupies a central role in the metabolism of extant organisms, as well as being implicated as the original genetic and catalytic macromolecule as formalized in the RNA World hypothesis. However, RNA is both structurally and chemically unstable, readily denaturing at high temperatures. In spite of this inherent instability, the existence of hyperthermophilic organisms demonstrates that solutions to the RNA stability problem have been found. Indeed, in contrast to the transfer RNA (tRNA) from mesophilic microorganisms, tRNA from thermophilic organisms possess remarkable thermal stability, a property hypothesized to be a consequence principally of chemical modification at specific positions in the RNA. Because tRNA requires a well-defined structure for its biological activity, it presents an ideal system in which to explore contemporary solutions to the problem of RNA stability, and to test mechanisms of imparting thermal stability potentially available to primitive organisms or primordial RNA. The objective of our proposed research is to test the hypothesis that archaeosine, a hypermodified nucleoside ubiquitous to the tRNA of the Archaea, is essential to the structural stability of tRNA in extant archaeal hyperthermophiles. Specifically we plan: 1) to determine if archaeosine imparts significant structural stability to otherwise thermally unstable tRNA, 2) to determine if structural analogs of archaeosine known to be synthesized under putative prebiotic conditions are capable of imparting thermal stability to otherwise thermally unstable tRNA, and 3) to investigate the role of archaeosine in vivo in Sulfolobus solfataricus, a hyperthermophilic archaeon.

The goals of this collaborative proposal build on the complementary strengths of the PI (a chemist/biochemist) and co-PI (a molecular biologist/virologist). The proposed work directly addresses NASA’s interest in understanding the origin and evolution of life in the Universe. In particular, our work addresses issues relating to the nature of the most primitive organisms and the environment in which they evolved. Whether the environment of the early earth was hot or organisms moved into hot environments as a consequence of niche expansion, elucidating the factors responsible for RNA stability of extant organisms inhabiting hydrothermal environments is central to understanding the structural requirements faced by primitive organisms in the early history of the Earth, as well as the replicating systems that predated the emergence of life on earth in the putative RNA World.