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Post-transcriptional Regulation
Post-transcriptional regulation is the control of gene expression at the RNA level. It occurs once the RNA polymerase has been attached to the gene's promoter and is synthesizing the nucleotide sequence. Therefore, as the name indicates, it occurs between the transcription phase and the translation phase of gene expression. These controls are critical for the regulation of many genes across human tissues. It also plays a big role in cell physiology, being implicated in pathologies such as cancer and neurodegenerative diseases. Mechanism After being produced, the stability and distribution of the different transcripts is regulated (post-transcriptional regulation) by means of RNA binding protein (RBP) that control the various steps and rates controlling events such as alternative splicing, nuclear degradation ( exosome), processing, nuclear export (three alternative pathways), sequestration in P-bodies for storage or degradation and ultimately translation. These proteins ac ...
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Gene Expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) and small nuclear RNA (snRNA), the product is a functional non-coding RNA. Gene expression is summarized in the central dogma of molecular biology first formulated by Francis Crick in 1958, further developed in his 1970 article, and expanded by the subsequent discoveries of reverse transcription and RNA replication. The process of gene expression is used by all known life—eukaryotes (including multicellular organisms), prokaryotes (bacteria and archaea), and utilized by viruses—to generate the macromolecular machinery for life. In genetics, gene expression is the most fundamental level at which the genotype gives rise to the phenotype, '' ...
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Directionality (molecular Biology)
Directionality, in molecular biology and biochemistry, is the end-to-end chemical orientation of a single strand of nucleic acid. In a single strand of DNA or RNA, the chemical convention of naming carbon atoms in the nucleotide pentose-sugar-ring means that there will be a 5′ end (usually pronounced "five-prime end"), which frequently contains a phosphate group attached to the 5′ carbon of the ribose ring, and a 3′ end (usually pronounced "three-prime end"), which typically is unmodified from the ribose -OH substituent. In a DNA double helix, the strands run in opposite directions to permit base pairing between them, which is essential for replication or transcription of the encoded information. Nucleic acids can only be synthesized in vivo in the 5′-to-3′ direction, as the polymerases that assemble various types of new strands generally rely on the energy produced by breaking nucleoside triphosphate bonds to attach new nucleoside monophosphates to the 3′- ...
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Rho Independent Termination
Intrinsic, or rho-independent termination, is a process in prokaryotes to signal the end of transcription and release the newly constructed RNA molecule. In prokaryotes such as E. coli, transcription is terminated either by a rho-dependent process or rho-independent process. In the Rho-dependent process, the rho-protein locates and binds the signal sequence in the mRNA and signals for cleavage. Contrarily, intrinsic termination does not require a special protein to signal for termination and is controlled by the specific sequences of RNA. When the termination process begins, the transcribed mRNA forms a stable secondary structure hairpin loop, also known as a Stem-loop. This RNA hairpin is followed by multiple uracil nucleotides. The bonds between uracil and adenine are very weak. A protein bound to RNA polymerase (nusA) binds to the stem-loop structure tightly enough to cause the polymerase to temporarily stall. This pausing of the polymerase coincides with transcription of the ...
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RNA Polymerase
In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the double-stranded DNA so that one strand of the exposed nucleotides can be used as a template for the synthesis of RNA, a process called transcription. A transcription factor and its associated transcription mediator complex must be attached to a DNA binding site called a promoter region before RNAP can initiate the DNA unwinding at that position. RNAP not only initiates RNA transcription, it also guides the nucleotides into position, facilitates attachment and elongation, has intrinsic proofreading and replacement capabilities, and termination recognition capability. In eukaryotes, RNAP can build chains as long as 2.4 million nucleotides. RNAP produces RNA that, functionally, is either for protein coding, i.e. messenger RNA (mRNA); or n ...
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Tryptophan Hydroxylase
Tryptophan hydroxylase (TPH) is an enzyme () involved in the synthesis of the neurotransmitter serotonin. Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin-dependent aromatic amino acid hydroxylases. TPH catalyzes the following chemical reaction : L-tryptophan + tetrahydrobiopterin + O2 \rightleftharpoons 5-Hydroxytryptophan + dihydrobiopterin + H2O It employs one additional cofactor, iron. Function It is responsible for addition of the -OH group (hydroxylation) to the 5 position to form the amino acid 5-hydroxytryptophan (5-HTP), which is the initial and rate-limiting step in the synthesis of the neurotransmitter serotonin. It is also the first enzyme in the synthesis of melatonin. Tryptophan hydroxylase (TPH), tyrosine hydroxylase (TH) and phenylalanine hydroxylase (PAH) are members of a superfamily of aromatic amino acid hydroxylases, catalyzing key steps in important metabolic pathways. Analogousl ...
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ADAR
Adar ( he, אֲדָר ; from Akkadian ''adaru'') is the sixth month of the civil year and the twelfth month of the religious year on the Hebrew calendar, roughly corresponding to the month of March in the Gregorian calendar. It is a month of 29 days. Names and Leap Years The month's name, like all the others from the Hebrew calendar, was adopted during the Babylonian captivity. In the Babylonian calendar the name was Araḫ Addaru or Adār ('Month of Adar'). In leap years, it is preceded by a 30-day intercalary month named Adar Aleph ( he, אדר א׳, Aleph being the first letter of the Hebrew alphabet), also known as "Adar Rishon" (''First Adar'') or "Adar I", and it is then itself called Adar Bet ( he, אדר ב׳, Bet being the second letter of the Hebrew alphabet, also known as "Adar Sheni" (''Second Adar'' or "Adar II"). Occasionally instead of Adar I and Adar II, "Adar" and "Ve'Adar" are used (Ve means 'and' thus: And-Adar). Adar I and II occur during February–March o ...
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RNA Editing
RNA editing (also RNA modification) is a molecular process through which some cells can make discrete changes to specific nucleotide sequences within an RNA molecule after it has been generated by RNA polymerase. It occurs in all living organisms and is one of the most evolutionarily conserved properties of RNAs. RNA editing may include the insertion, deletion, and base substitution of nucleotides within the RNA molecule. RNA editing is relatively rare, with common forms of RNA processing (e.g. splicing, 5'-capping, and 3'-polyadenylation) not usually considered as editing. It can affect the activity, localization as well as stability of RNAs, and has been linked with human diseases. RNA editing has been observed in some tRNA, rRNA, mRNA, or miRNA molecules of eukaryotes and their viruses, archaea, and prokaryotes. RNA editing occurs in the cell nucleus, as well as within mitochondria and plastids. In vertebrates, editing is rare and usually consists of a small number of changes t ...
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EIF4G
Eukaryotic translation initiation factor 4 G (eIF4G) is a protein involved in eukaryotic translation initiation and is a component of the eIF4F cap-binding complex. Orthologs of eIF4G have been studied in multiple species, including humans, yeast, and wheat. However, eIF4G is exclusively found in domain Eukarya, and not in domains Bacteria or Archaea, which do not have capped mRNA. As such, eIF4G structure and function may vary between species, although the human EIF4G1 has been the focus of extensive studies. (Other human paralogs are EIF4G2 and EIF4G3.) Across species, eIF4G strongly associates with eIF4E, the protein that directly binds the mRNA cap. Together with the RNA helicase protein eIF4A, these form the eIF4F complex. Within the cell eIF4G is found primarily in the cytoplasm, usually bound to eIF4E; however, it is also found in the nucleus, where its function is unknown. It may have a role in nonsense-mediated decay. History eIF4G stands for eukaryotic initiation fac ...
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EIF4E
Eukaryotic translation initiation factor 4E, also known as eIF4E, is a protein that in humans is encoded by the ''EIF4E'' gene. Structure and function Most eukaryotic cellular mRNAs are blocked at their 5'-ends with the 7-methyl-guanosine five-prime cap structure, m7GpppX (where X is any nucleotide). This structure is involved in several cellular processes including enhanced translational efficiency, splicing, mRNA stability, and RNA nuclear export. eIF4E is a eukaryotic translation initiation factor involved in directing ribosomes to the cap structure of mRNAs. It is a 24-kD polypeptide that exists as both a free form and as part of the eIF4F pre-initiation complex. Almost all cellular mRNA require eIF4E in order to be translated into protein. The eIF4E polypeptide is the rate-limiting component of the eukaryotic translation apparatus and is involved in the mRNA-ribosome binding step of eukaryotic protein synthesis. The other subunits of eIF4F are a 47-kD polypeptide, terme ...
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Poly(A)-binding Protein
Poly(A)-binding protein (PAB or PABP) is an RNA-binding protein which triggers the binding of eukaryotic initiation factor 4 complex (eIF4G) directly to the poly(A) tail of mRNA which is 200-250 nucleotides long. The poly(A) tail is located on the 3' end of mRNA and was discovered by Mary Edmonds, who also characterized the poly-A polymerase enzyme that generates the poly(a) tail. The binding protein is also involved in mRNA precursors by helping polyadenylate polymerase add the poly(A) nucleotide tail to the pre-mRNA before translation. The nuclear isoform selectively binds to around 50 nucleotides and stimulates the activity of polyadenylate polymerase by increasing its affinity towards RNA. Poly(A)-binding protein is also present during stages of mRNA metabolism including nonsense-mediated decay and nucleocytoplasmic trafficking. The poly(A)-binding protein may also protect the tail from degradation and regulate mRNA production. Without these two proteins in-tandem, then the po ...
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Half-life
Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable atoms survive. The term is also used more generally to characterize any type of exponential (or, rarely, non-exponential) decay. For example, the medical sciences refer to the biological half-life of drugs and other chemicals in the human body. The converse of half-life (in exponential growth) is doubling time. The original term, ''half-life period'', dating to Ernest Rutherford's discovery of the principle in 1907, was shortened to ''half-life'' in the early 1950s. Rutherford applied the principle of a radioactive element's half-life in studies of age determination of rocks by measuring the decay period of radium to lead-206. Half-life is constant over the lifetime of an exponentially decaying quantity, and it is a characteristic unit for ...
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Intron
An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene... must be replaced by that of a transcription unit containing regions which will be lost from the mature messenger – which I suggest we call introns (for intragenic regions) – alternating with regions which will be expressed – exons." (Gilbert 1978) The term ''intron'' refers to both the DNA sequence within a gene and the corresponding RNA sequence in RNA transcripts. The non-intron sequences that become joined by this RNA processing to form the mature RNA are called exons. Introns are found in the genes of most organisms and many viruses and they can be located in both protein-coding genes and genes that function as RNA (noncoding genes). There are four main types of introns: tRNA introns, group I introns, group II introns, and ...
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