Effects of Molecular Crowding on Structures and Functions of Nucleic Acids

Abstract

More than half a century has passed since Francis Crick proposed the concept of “Central Dogma” and a sequence hypothesis, which are the fundamental bases of the life system. The term “gene” was coined by Gregor Johann Mendel for a factor that can transmit information over biological generations and defines the phenotypes of organisms. The main identity of “gene” as a physical material is DNA, and the word “gene” is often used to refer to the DNA region that encodes a protein and the region involved in the modulation of protein expression. Modulation of gene expression could occur in any reaction process in the central dogma such as at the transcriptional, posttranscriptional, translational, or posttranslational level. Since proteins were hitherto considered as molecules responsible for modulation, recognition mechanisms of nucleic acids (DNA and RNA) by proteins have been generally focused on to unveil detailed molecular mechanisms of the modulation process. In addition to proteins, DNA and RNA are macromolecules consisting of linearly polymerized monomer units, adenine (A), guanine (G), cytosine (C), and thymine (T) [or uracil (U) in RNA], that form secondary and tertiary structures based on the nucleotide sequence. Although nucleic acids have been thought to be simply recognized by proteins, it is becoming clear that they contribute actively to the modulation of gene expression based on their tertiary structures and stabilities. The structures and stabilities of nucleic acids are influenced by the surrounding molecular environment. In particular, the molecular environment in cells is characterized by high concentrations of biomolecules, which is known to create a crowding environment. Because the modulation of gene expression based on the structures and stabilities of nucleic acids have been optimized to function in such a crowding molecular environment, it is important to understand the behaviors of nucleic acids in the crowding environment. In this chapter, the effects of molecular crowding environments on the structures, stabilities, and functions of nucleic acids are discussed, with emphasis on the effects provided by physicochemical properties under the crowding environments that are different from those in a diluted aqueous solution.