RNA
Cellular organisms use messenger RNA (mRNA) to convey genetic information (using the nitrogenous bases of guanine, uracil, adenine, and cytosine, denoted by the letters G, U, A, and C) that directs synthesis of specific proteins.
Some RNA molecules play an active role within cells by catalyzing biological reactions, controlling gene expression, or sensing and communicating responses to cellular signals.
[10] An important structural component of RNA that distinguishes it from DNA is the presence of a hydroxyl group at the 2' position of the ribose sugar.
The presence of this functional group causes the helix to mostly take the A-form geometry,[11] although in single strand dinucleotide contexts, RNA can rarely also adopt the B-form most commonly observed in DNA.
[13] A second consequence of the presence of the 2'-hydroxyl group is that in conformationally flexible regions of an RNA molecule (that is, not involved in formation of a double helix), it can chemically attack the adjacent phosphodiester bond to cleave the backbone.
[14] The functional form of single-stranded RNA molecules, just like proteins, frequently requires a specific spatial tertiary structure.
Certain RNAs are able to catalyse chemical reactions such as cutting and ligating other RNA molecules,[33] and the catalysis of peptide bond formation in the ribosome;[10] these are known as ribozymes.
It has sites for amino acid attachment and an anticodon region for codon recognition that binds to a specific sequence on the messenger RNA chain through hydrogen bonding.
[44] Fire and Mello were awarded the 2006 Nobel Prize in Physiology or Medicine for discovering microRNAs (miRNAs), specific short RNA molecules that can base-pair with mRNAs.
Their roles, at first mysterious, were shown by Jeannie T. Lee and others to be the silencing of blocks of chromatin via recruitment of Polycomb complex so that messenger RNA could not be transcribed from them.
[55] The CRISPR system, recently being used to edit DNA in situ, acts via regulatory RNAs in archaea and bacteria to provide protection against virus invaders.
In eukaryotes, modifications of RNA nucleotides are in general directed by small nucleolar RNAs (snoRNA; 60–300 nt),[32] found in the nucleolus and cajal bodies.
Viroids are another group of pathogens, but they consist only of RNA, do not encode any protein and are replicated by a host plant cell's polymerase.
[68][69][70][71] In eukaryotes, double-stranded RNA (dsRNA) plays a role in the activation of the innate immune system against viral infections.
[72] In the late 1970s, it was shown that there is a single stranded covalently closed, i.e. circular form of RNA expressed throughout the animal and plant kingdom (see circRNA).
[73] circRNAs are thought to arise via a "back-splice" reaction where the spliceosome joins a upstream 3' acceptor to a downstream 5' donor splice site.
[75] Severo Ochoa won the 1959 Nobel Prize in Medicine (shared with Arthur Kornberg) after he discovered an enzyme that can synthesize RNA in the laboratory.
In the early 1970s, retroviruses and reverse transcriptase were discovered, showing for the first time that enzymes could copy RNA into DNA (the opposite of the usual route for transmission of genetic information).
[79] In 1977, introns and RNA splicing were discovered in both mammalian viruses and in cellular genes, resulting in a 1993 Nobel to Philip Sharp and Richard Roberts.
Catalytic RNA molecules (ribozymes) were discovered in the early 1980s, leading to a 1989 Nobel award to Thomas Cech and Sidney Altman.
[83] Adding to the Nobel prizes for research on RNA, in 2009 it was awarded for the elucidation of the atomic structure of the ribosome to Venki Ramakrishnan, Thomas A. Steitz, and Ada Yonath.
In 2023 the Nobel Prize in Physiology or Medicine was awarded to Katalin Karikó and Drew Weissman for their discoveries concerning modified nucleosides that enabled the development of effective mRNA vaccines against COVID-19.
[87][88] In May 2022, scientists discovered that RNA can form spontaneously on prebiotic basalt lava glass, presumed to have been abundant on the early Earth.
[89][90] In March 2015, DNA and RNA nucleobases, including uracil, cytosine and thymine, were reportedly formed in the laboratory under outer space conditions, using starter chemicals such as pyrimidine, an organic compound commonly found in meteorites.
Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), is one of the most carbon-rich compounds found in the universe and may have been formed in red giants or in interstellar dust and gas clouds.
[91] In July 2022, astronomers reported massive amounts of prebiotic molecules, including possible RNA precursors, in the galactic center of the Milky Way Galaxy.
Therapeutic applications arise as RNA folds into complex conformations and binds proteins, nucleic acids, and small molecules to form catalytic centers.
Ribavirin, branaplam, and ataluren are currently available medications that stabilize double-stranded RNA structures and control splicing in a variety of disorders.
[97] In vitro transcribed mRNAs (IVT-mRNA) have been used to deliver proteins for bone regeneration, pluripotency, and heart function in animal models.
[98][99][100][101][102] SiRNAs, short RNA molecules, play a crucial role in innate defense against viruses and chromatin structure.
