The Expanding View of RNA and DNA Function

Abstract

Summary RNA and DNA are simple linear polymers consisting of only four major types of subunits, and yet these molecules carry out a remarkable diversity of functions in cells and in the laboratory. Each newly-discovered function of natural or engineered nucleic acids enforces the view that prior assessments of nucleic acid function were far too narrow and that many more exciting findings are yet to come. This Perspective highlights just a few of the numerous discoveries over the past 20 years pertaining to nucleic acid function, focusing on those that have been of particular interest to chemical biologists. History suggests that there will continue to be many opportunities to engage chemical biologists in the discovery, creation, and manipulation of nucleic acid function in the years to come.

MicroRNA‐135a‐3p as a promising biomarker and nucleic acid therapeutic agent for ovarian cancer

“…DNA and RNA are simple linear polymers that have moved into the realm of stand‐alone therapeutic agents for a variety of human diseases . Several types of RNA molecules with complex biological functions, including mRNA, transfer RNA, miRNA, and siRNA, have been discovered, while major chemical modifications in siRNA and miRNA have been identified, including the ribose 2′‐OH group modification, locked and unlocked nucleic acids, and phosphorothioate modification, leading to a diverse range of therapeutic applications for human diseases . Based on these findings, clinical trials of siRNA‐ and miRNA‐based drugs have already been initiated .…”

Directed evolution of artificial enzymes (XNAzymes) from diverse repertoires of synthetic genetic polymers

“…Option Therefore, if the library design (or limitations in preparation) is such that a very low level of activity is expected (e.g., a highly diverse XNA repertoire is synthesized, representing a sparse sampling of sequence space), or an XNA system with a higher error rate is used, then longer incubation times (days) or more favorable reaction conditions for the chosen chemistry (e.g., higher temperature, pH, divalent cation concentrations) could be used for initial selection rounds (e.g., several days in rounds 1-5), and then stringency could be increased later on (e.g., several hours in rounds 5-15, several minutes in round [15][16][17][18][19][20]. This approach aims to increase the number of catalytic molecules recovered early on, thus allowing enrichment when active sequences are rare, and then later on selecting for (or evolving through point mutation, in an analogous manner to antibody affinity maturation) the most active.…”

Bautechnik aktuell 11/2014

“…The next level would be to search for “fitness landscapes”63 within the chimeric backbone and heterogeneous‐sequence space for systems that would be conducive to the rise of a homogeneous system, perhaps via Darwinian evolution. The enormous amount of molecular biology experiments that have been performed to give credence to the RNA world hypothesis, and the successful extension of such experiments to XNAs, give reasonable hope that such techniques64 could be brought to bear on the chimeric backbones of the “pre‐RNA world” as well.…”