User:Sunita George/RNA world

RNA as an enzyme
In the 1980s, RNA structures capable of self-processing were discovered, with the RNA moiety of RNase P acting as its catalytic subunit. These catalytic RNAs were referred to as RNA enzymes, or ribozymes and are found in today's DNA-based life and could be examples of living fossils. Ribozymes play vital roles, such as that of the ribosome. The large subunit of the ribosome includes an rRNA responsible for the peptide bond-forming peptidyl transferase activity of protein synthesis. Many other ribozyme activities exist; for example, the hammerhead ribozyme performs self-cleavage and an RNA polymerase ribozyme can synthesize a short RNA strand from a primed RNA template.

Among the enzymatic properties important for the beginning of life are:

Cofactors

Protein enzymes catalyze various chemical reactions, but over half of them incorporate cofactors to facilitate and diversify their catalytic activities. Cofactors are essential in biology, as they are based largely on nucleotides rather than amino acids. Ribozymes use nucleotide cofactors to create metabolism, with two basic choices: non-covalent binding or covalent attachment. Both approaches have been demonstrated using directed evolution to reinvent RNA dupes of protein-catalyzed processes. Lorsch and Szostak investigated ribozymes that could phosphorylate themselves and use ATP-γS as a substrate. However, only one of the seven classes of selected ribozymes had detectable ATP affinity, indicating that the ability to bind ATP was compromised. NAD+- dependent redox ribozymes were also evaluated. The select ribozyme had a rate of enhancement of more than 107 fold and was proven to catalyze the reverse reaction - benzaldehyde reduction by NADH. Since the usage of adenosine as a cofactor is prevalent in current metabolism and is likely to have been common in the RNA world, these discoveries are essential for the evolution of metabolism in the RNA world.

RNA in Therapeutics

RNA, initially deemed unsuitable for therapeutic use due to its short half-life, has been proven to possess numerous therapeutic properties through advancements in stabilization chemistry. RNA molecules have potential therapeutic applications due to their ability to fold into complex conformations and binding proteins, nucleic acids, small molecules, and form catalytic centers. RNA-based vaccines are thought to be a quicker way to obtain immunological resistance than the traditional approach of vaccines that rely on a killed or altered version of the pathogen, because it can take months or even years to grow and study a pathogen in order to determine which molecular parts to extract, inactivate, and use in a vaccine. Small molecules with conventional therapeutic properties can target RNA and DNA structures, thereby treating novel diseases. However, research on small molecules targeting RNA and approved drugs for human illness therapy is scarce. Ribavirin, branaplam, and ataluren are currently available medications that stabilize double-stranded RNA structures and control splicing in a variety of disorders. Protein-coding mRNAs have emerged as new therapeutic candidates, with RNA replacement being particularly beneficial for brief but torrent-like protein expression. In vitro transcribed mRNAs (IVT-mRNA) have been used to deliver proteins for bone regeneration, pluripotency, and heart function in animal models. SiRNAs, short RNA molecules, play a crucial role in innate defense against viruses and chromatin structure. They can be artificially introduced to silence specific genes, making them valuable for gene function studies, therapeutic target validation, and drug development.