> See also: > - [[Nucleic Acids]] > - [[Post-Translational Modifications]] # Ribonucleic Acid (RNA) ## Major Types of RNA **Non-Coding RNAs** - Introns (transcribed from DNA but not part of protein-coding regions) - Ribosomal RNA (rRNA) - Transfer RNA (tRNA) - Micro RNA (miRNA) - Short Interfering RNA (siRNA) - Riboswitches ### Ribonucleases (RNase) **RNase (ribonuclease) A** is a single-strand specific endoribonuclease found abundantly in tissues and cells (hard to avoid being present). - Resistant to metal chelating agents - Can survive prolonged boiling or autoclaving ### Transfer RNA (tRNA) The amino acid attaches to the 3’ strand of the acceptor stem on tRNA molecules ![[Pasted image 20240201034020.png|300]] ### Ribosomal RNA (rRNA) ## Interference RNA (RNAi) Overview: 1. RNA Structure 2. RNA Function ## Major Differences vs DNA - The new 2’ -OH group present inhibits the natural helical formation and supports chemical degradation of the molecule Typically is found single stranded, but whenever it is double stranded it is called *A-form RNA* due to the additional hydroxyl group causing steric hinderance (similar yet slightly different than DNA’s A-form) - “Not as clean/crisp/repetitive as it is with DNA” While we say RNA is “*typically single stranded*”, it makes sense from a thermodynamic perspective that the bases present would still want to bind to something and maintain as many H-bonds as possible → - Nothing is stopping these bases from forming H-bonds with water, however, because the complementary base pairings are so much stronger (and more specific), gradually all of the molecules within a system will - Similar concept to the hydrophobic effect While the glycosidic bonds were revealed to be cis, and therefore antiparallel in nature, RNA molecules they can be either cis or trans (parallel) - This means that dsRNA can be parallel as well as antiparallel ### Unique Bases & Base Pairings **Inosine** is a precursor to the canonical purine nitrogen bases, but it can also serve as a base itself present within molecules of RNA Due to the generally reduced “uniformity” of dsRNA, a wider variety of base pairings can be observed - [[Nucleic Acids]] The **wobble position** of a codon refers to the 3rd nucleotide in a codon. - Binding of the mRNA codon to the cognate tRNA is much “looser” at this position - The genetic code is redundant, meaning that certain codons encode for the same amino acid. This redundancy is often specified in this 3rd nucleotide position. ## Secondary Structure of RNA - Bulges, loops, hairpins The potential secondary structures of RNA are far more The goal is to maximize the amount of hydrogen bondings and leave as few unpaired bases as possible The presence of the 2’ hydroxyl allows for additional hydrogen bonding to help stabilize these structures - However, it also has the potential to attack the nearby phosphate bond, cleaving the RNA strand in the process. (Known as “auto-catalytic breakdown”) Both proteins and RNA share many similarities during their folding process - Goal is to move towards “global minimum” where weak interactions (H-bonds) are maximized and free energy (potential) is minimized ![[Pasted image 20240225043604.png|300]] https://eternagame.org/puzzles/11098076/play ## Tertiary Structure of RNA ### tRNA Folding tRNA forms a cloverleaf structure as a result of base stacking, H-bonds, and non-Watson-Crick base pairings 72/76 base paired are involved with base stacking - tRNA molecules are a single transcript - We have hundreds of variations of these within our genome - Mitochondrial genes also contain their own unique tRNA The only unpaired bases within tRNA molecules are found within the anticodon region and the acceptor arm which binds to the corresponding amino acid ## RNA Function **Ribozyme:** an RNA molecule capable of catalyzing a chemical reaction Ribozymes can have multiple domains and *function similarly to proteins/enzymes* - Proteins have significantly more variability due to the amount of amino acids\ - Meanwhile RNA only has the 4 primary base pairs. While there are many derivatives/variations of these, they are still fundamentally similar in many ways and don’t differ to the degree that amino acids do (hydrophobic vs polar charged vs polar uncharged) **Regulation** - microRNA (miRNA) - small interfering RNA (siRNA) - riboswitches, RNase P (generates tRNAs), spliceosome, hammerhead, introns ![[Pasted image 20240225061330.png|300]] **Hammerhead Ribozyme** - The catalytic pocket is “held open” due to the presence of non-complementary base pair alignment **Riboswitches** - Control gene expression in response to changes in the concentration of metabolites - Typically found within the 5’ untranslated regions (5’-UTRs) - Essentially, conformational changes are induced by the presence of a metabolite which is capable of inducing a secondary structure motif forming closer to the gene sequence that inhibits translation I absolutely hate the fact that there is a riboswitch for guanine… - same energy as hemoglobin being composed of a shit ton of oxygens but can only transport 4 friendship ended with …, Diaminomaleonitrile (DAMN) is my new favorite molecule