Prebiotic RNA self-assembling and the origin of life: Mechanistic and molecular modeling rationale for explaining the prebiotic origin and replication of RNA

In recent years, a great interest has been focused on the prebiotic origin of nucleic acids and life on Earth. An attractive idea is that life was initially based on an autocatalytic and autoreplicative RNA (the RNA-world). RNA duplexes are right-handed helical chains with antiparallel orientation, but the rationale for these features is not yet known. An antiparallel (inverted) stacking of purine nucleosides was reported in crystallographic studies. Molecular modeling also supports the inverted orientation of nucleosides. This preferential stacking can also appear when nucleosides are included in a montmorillonite clay matrix. Free-energy values and geometrical parameters show that D-ribose chirality is preferred for the formation of right-handed RNA molecules. Thus, a "zipper" model with antiparallel and auto-intercalated nucleosides linked by phosphate groups can be proposed to form single RNA chains. Unstacking with strand separation and base pairing by H-bonding, results in shortening and inclination of ribose-phosphate chains, leading to right-handed helicity and antiparallel duplexes. Incorporation of complementary precursors on the major groove template by a self-assembly mechanism provides a prebiotic (non-enzymatic) "tetris" replication model by formation of a transient RNA tetrad and tetraplex. Original hairpin motifs appear as simple building units that form typical RNA structures such as hammerheads, cloverleaves and dumbbells. They occur today in the circular viroids and virusoids, as well as in highly branched and complex rRNA molecules.