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Polymerase Stuttering
Polymerase stuttering is the process by which a polymerase transcribes a nucleotide several times without progressing further on the mRNA chain. It is often used in addition of poly A tails or capping mRNA chains by less complex organisms such as viruses. Process A polymerase may undergo stuttering as a probability controlled event, hence it is not explicitly controlled by any mechanisms in the translation process. Generally, it is a result of many short repeated frameshifts on a slippery sequence of nucleotides on the mRNA strand. However, the frameshift is restricted to one (in some cases two) nucleotides with a pseudoknot or choke points on both sides of the sequence. Examples A polymerase that exhibits this behavior is RNA-dependent RNA polymerase, present in many RNA viruses. Reverse transcriptase A reverse transcriptase (RT) is an enzyme used to convert RNA genome to DNA, a process termed reverse transcription. Reverse transcriptases are used by viruses such ...
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Polymerase
In biochemistry, a polymerase is an enzyme (Enzyme Commission number, EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using Base pair, base-pairing interactions or RNA by half ladder replication. A DNA polymerase from the thermophile, thermophilic bacterium, ''Thermus aquaticus'' (''Taq'') (Protein Data Bank, PDB]1BGX EC 2.7.7.7) is used in the polymerase chain reaction, an important technique of molecular biology. A polymerase may be template-dependent or template-independent. Polynucleotide adenylyltransferase, Poly-A-polymerase is an example of template independent polymerase. Terminal deoxynucleotidyl transferase also known to have template independent and template dependent activities. By function *DNA polymerase (DNA-directed DNA polymerase, DdDP) **Family A: DNA polymerase I; Pol POLG, γ, POLQ, θ, DNA polymer ...
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Transcription (genetics)
Transcription is the process of copying a segment of DNA into RNA for the purpose of gene expression. Some segments of DNA are transcribed into RNA molecules that can encode proteins, called messenger RNA (mRNA). Other segments of DNA are transcribed into RNA molecules called non-coding RNAs (ncRNAs). Both DNA and RNA are nucleic acids, which use base pairs of nucleotides as a complementary language. During transcription, a DNA sequence is read by an RNA polymerase, which produces a complementary, antiparallel RNA strand called a primary transcript. In virology, the term transcription is used when referring to mRNA synthesis from a viral RNA molecule. The genome of many RNA viruses is composed of negative-sense RNA which acts as a template for positive sense viral messenger RNA - a necessary step in the synthesis of viral proteins needed for viral replication. This process is catalyzed by a viral RNA dependent RNA polymerase. Background A DNA transcription unit encoding ...
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MRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is created during the process of Transcription (biology), transcription, where an enzyme (RNA polymerase) converts the gene into primary transcript mRNA (also known as pre-mRNA). This pre-mRNA usually still contains introns, regions that will not go on to code for the final amino acid sequence. These are removed in the process of RNA splicing, leaving only exons, regions that will encode the protein. This exon sequence constitutes mature mRNA. Mature mRNA is then read by the ribosome, and the ribosome creates the protein utilizing amino acids carried by transfer RNA (tRNA). This process is known as Translation (biology), translation. All of these processes form part of the central dogma of molecular biology, which describes the flow of geneti ...
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Poly A Tail
Polyadenylation is the addition of a poly(A) tail to an RNA transcript, typically a messenger RNA (mRNA). The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In eukaryotes, polyadenylation is part of the process that produces mature mRNA for translation. In many bacteria, the poly(A) tail promotes degradation of the mRNA. It, therefore, forms part of the larger process of gene expression. The process of polyadenylation begins as the transcription of a gene terminates. The 3′-most segment of the newly made pre-mRNA is first cleaved off by a set of proteins; these proteins then synthesize the poly(A) tail at the RNA's 3′ end. In some genes these proteins add a poly(A) tail at one of several possible sites. Therefore, polyadenylation can produce more than one transcript from a single gene (alternative polyadenylation), similar to alternative splicing. The poly(A) tail is important for the nuclea ...
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5' Cap
In molecular biology, the five-prime cap (5′ cap) is a specially altered nucleotide on the 5′ end of some primary transcripts such as precursor messenger RNA. This process, known as mRNA capping, is highly regulated and vital in the creation of stable and mature messenger RNA able to undergo translation during protein synthesis. Mitochondrial mRNA and chloroplastic mRNA are not capped. Structure In eukaryotes, the 5′ cap (cap-0), found on the 5′ end of an mRNA molecule, consists of a guanine nucleotide connected to mRNA via an unusual 5′ to 5′ triphosphate linkage. This guanosine is methylated on the 7 position directly after capping ''in vivo'' by a methyltransferase. It is referred to as a 7-methylguanylate cap, abbreviated m7G. The Cap-0 is the base cap structure, however, the first and second transcribed nucleotides can also be 2' O-methylated, leading to the Cap-1 and Cap-2 structures, respectively. This is more common in higher eukaryotes an ...
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Organism
An organism is any life, living thing that functions as an individual. Such a definition raises more problems than it solves, not least because the concept of an individual is also difficult. Many criteria, few of them widely accepted, have been proposed to define what an organism is. Among the most common is that an organism has autonomous reproduction, Cell growth, growth, and metabolism. This would exclude viruses, despite the fact that they evolution, evolve like organisms. Other problematic cases include colonial organisms; a colony of eusocial insects is organised adaptively, and has Germ-Soma Differentiation, germ-soma specialisation, with some insects reproducing, others not, like cells in an animal's body. The body of a siphonophore, a jelly-like marine animal, is composed of organism-like zooids, but the whole structure looks and functions much like an animal such as a jellyfish, the parts collaborating to provide the functions of the colonial organism. The evolutiona ...
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Probability
Probability is a branch of mathematics and statistics concerning events and numerical descriptions of how likely they are to occur. The probability of an event is a number between 0 and 1; the larger the probability, the more likely an event is to occur."Kendall's Advanced Theory of Statistics, Volume 1: Distribution Theory", Alan Stuart and Keith Ord, 6th ed., (2009), .William Feller, ''An Introduction to Probability Theory and Its Applications'', vol. 1, 3rd ed., (1968), Wiley, . This number is often expressed as a percentage (%), ranging from 0% to 100%. A simple example is the tossing of a fair (unbiased) coin. Since the coin is fair, the two outcomes ("heads" and "tails") are both equally probable; the probability of "heads" equals the probability of "tails"; and since no other outcomes are possible, the probability of either "heads" or "tails" is 1/2 (which could also be written as 0.5 or 50%). These concepts have been given an axiomatic mathematical formaliza ...
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Ribosomal Frameshift
Ribosomal frameshifting, also known as translational frameshifting or translational recoding, is a biological phenomenon that occurs during translation that results in the production of multiple, unique proteins from a single mRNA. The process can be programmed by the nucleotide sequence of the mRNA and is sometimes affected by the secondary, 3-dimensional mRNA structure. It has been described mainly in viruses (especially retroviruses), retrotransposons and bacterial insertion elements, and also in some cellular genes. Small molecules, proteins, and nucleic acids have also been found to stimulate levels of frameshifting. In December 2023, it was reported that ''in vitro''-transcribed (IVT) mRNAs in response to BNT162b2 (Pfizer–BioNTech) anti-COVID-19 vaccine caused ribosomal frameshifting. Process overview Proteins are translated by reading tri-nucleotides on the mRNA strand, also known as codons, from one end of the mRNA to the other (from the 5' to the 3' end) starting wi ...
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Nucleotide
Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all Life, life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common Nutrient, nutrients by the liver. Nucleotides are composed of three subunit molecules: a nucleobase, a pentose, five-carbon sugar (ribose or deoxyribose), and a phosphate group consisting of one to three phosphates. The four nucleobases in DNA are guanine, adenine, cytosine, and thymine; in RNA, uracil is used in place of thymine. Nucleotides also play a central role in metabolism at a fundamental, cellular level. They provide chemical energy—in the form of the nucleoside triphosphates, adenosine triphosphate (ATP), guanosine triphosphate (GTP), cytidine triphosphate (CTP), and uridine triph ...
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Pseudoknot
__NOTOC__ A pseudoknot is a nucleic acid secondary structure containing at least two stem-loop structures in which half of one stem is intercalated between the two halves of another stem. The pseudoknot was first recognized in the turnip yellow mosaic virus in 1982. Pseudoknots fold into knot-shaped three-dimensional conformations but are not true topological knots. These structures are categorized as cross (X) topology within the circuit topology framework, which, in contrast to knot theory, is a contact-based approach. Prediction and identification The structural configuration of pseudoknots does not lend itself well to bio-computational detection due to its context-sensitivity or "overlapping" nature. The base pairing in pseudoknots is not well nested; that is, base pairs occur that "overlap" one another in sequence position. This makes the presence of pseudoknots in RNA sequences more difficult to predict by the standard method of dynamic programming, which use a recur ...
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Choke Point
In military strategy, a choke point (or chokepoint), or sometimes bottleneck, is a geographical feature on land such as a valley, defile or bridge, or maritime passage through a critical waterway such as a strait, which an armed force is forced to pass through in order to reach its objective, sometimes on a substantially narrowed front and therefore greatly decreasing its combat effectiveness by making it harder to bring superior numbers to bear. A choke point can allow a numerically inferior defending force to use the terrain as a force multiplier to thwart or ambush a much larger opponent, as the attacker cannot advance any further without first securing passage through the choke point. Historical examples Some historical examples of the tactical use of choke points are King Leonidas I's defense of the Pass of Thermopylae during an invasion led by Xerxes I of Persia; the Battle of Stamford Bridge in which Harold Godwinson defeated Harald Hardrada; William Wallace' ...
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RNA-dependent RNA Polymerase
RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the self-replication, replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand Complementarity (molecular biology), complementary to a given RNA template. This is in contrast to typical DNA-dependent RNA polymerases, which all organisms use to catalyze the transcription (genetics), transcription of RNA from a DNA template. RdRp is an essential protein encoded in the genomes of most RNA-containing viruses that lack a DNA stage, including SARS-CoV-2. Some eukaryotes also contain RdRps, which are involved in RNA interference and differ structurally from viral RdRps. History Viral RdRps were discovered in the early 1960s from studies on mengovirus and polio virus when it was observed that these viruses were not sensitive to actinomycin D, a drug that inhibits cellular DNA-directed RNA synthesis. This lack of sensitivity suggested the action of a virus-specific ...
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