Exobiology and Evolutionary Biology

Measuring the abundance of the simplest functional RNAs (2)

PI: Robin Knight

This substantially revised proposal addresses Objective 3.2 of the NASA Astrobiology Road Map, “Origins and evolution of functional biomolecules”, by developing new tools to estimate the abundance of the simplest types of functional RNA molecules. RNA (RiboNucleic Acid), a biomolecule similar to DNA, plays several key roles in modern cells and is widely believed to have preceded DNA as a genetic material. Of particular interest, very short RNAs (fewer than 30 nucleotides) that consist of active sites assembled from conserved modules separated by essentially random spacer have been demonstrated to perform a range of biochemical functions, including catalysis and binding.
The expanding list of functional roles that RNA is known to play in modern cells, and the expanding range of catalytic activities that RNA can perform in the lab, raise two fascinating questions. Was there a stage of evolution when RNA was the primary catalyst? Are modern functional RNAs holdovers from this RNA world? To answer these questions, we need to understand how easily functional RNAs, i.e. sequences that can catalyze a reaction or bind a substrate, can emerge from pools of random sequences.
We have made several empirical observations and technical advances that allow us to measure the abundance of functional RNA sequences at a specified level of activity. In this proposal, we focus on 3D modeling and experimental characterization of the
information content of RNA active sites, which we will complement with statistical analyses that compare RNA sequences across large groups of organisms.