Polyadenylation
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Polyadenylation
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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MRNA Structure
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, utilising amino acids carried by transfer RNA (tRNA), the ribosome creates the protein. 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 genet ...
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Messenger RNA
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 synthesizing a protein. mRNA is created during the process of 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, utilising amino acids carried by transfer RNA (tRNA), the ribosome creates the protein. This process is known as translation. All of these processes form part of the central dogma of molecular biology, which describes the flow of genetic information in a biological system. As in DNA, genetic inf ...
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Cleavage And Polyadenylation Specificity Factor
Cleavage and polyadenylation specificity factor (CPSF) is involved in the cleavage of the 3' signaling region from a newly synthesized pre-messenger RNA (pre-mRNA) molecule in the process of gene transcription. It is the first protein to bind to the signaling region near the cleavage site of the pre-mRNA, to which the poly(A) tail will be added by polynucleotide adenylyltransferase. The upstream signaling region has the canonical nucleotide sequence AAUAAA, which is highly conserved across the vast majority of pre-mRNAs. A second downstream signaling region, located on the portion of the pre-mRNA that is cleaved before polyadenylation, consists of a GU-rich region required for efficient processing. Structure CPSF is a protein complex, consisting of four proteins: CPSF-73, CPSF-100, CPSF-30 and CPSF-160. CPSF-73 is a zinc-dependent hydrolase which cleaves the mRNA precursor just downstream the polyadenylation signal sequence AAUAAA. CPSF-160 is the largest subunit of CPSF and d ...
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Long Noncoding RNA
Long non-coding RNAs (long ncRNAs, lncRNA) are a type of RNA, generally defined as transcripts more than 200 nucleotides that are not translated into protein. This arbitrary limit distinguishes long ncRNAs from small non-coding RNAs, such as microRNAs (miRNAs), small interfering RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), and other short RNAs. Long intervening/intergenic noncoding RNAs (lincRNAs) are sequences of lncRNA which do not overlap protein-coding genes. Long non-coding RNAs include intergenic lincRNAs, intronic ncRNAs, and sense and antisense lncRNAs, each type showing different genomic positions in relation to genes and exons. Abundance In 2007 a study found only one-fifth of transcription across the human genome is associated with protein-coding genes, indicating at least four times more long non-coding than coding RNA sequences. Large-scale complementary DNA (cDNA) sequencing projects such as FANTOM reveal the complexity of this tr ...
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Alternative Splicing
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA (mRNA) produced from that gene. This means the exons are joined in different combinations, leading to different (alternative) mRNA strands. Consequently, the proteins translated from alternatively spliced mRNAs will contain differences in their amino acid sequence and, often, in their biological functions (see Figure). Biologically relevant alternative splicing occurs as a normal phenomenon in eukaryotes, where it increases the number of proteins that can be encoded by the genome. In humans, it is widely believed that ~95% of multi-exonic genes are alternatively spliced to produce functional alternative products from the same gene but many scientists believe that most o ...
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MicroRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRNAs base-pair to complementary sequences in mRNA molecules, then gene silence said mRNA molecules by one or more of the following processes: (1) cleavage of mRNA strand into two pieces, (2) destabilization of mRNA by shortening its poly(A) tail, or (3) translation of mRNA into proteins. This last method of gene silencing is the least efficient of the three, and requires the aid of ribosomes. miRNAs resemble the small interfering RNAs (siRNAs) of the RNA interference (RNAi) pathway, except miRNAs derive from regions of RNA transcripts that fold back on themselves to form short hairpins, whereas siRNAs derive from longer regions of double-stranded RNA. The human genome may encode over 1900 miRNAs, although more recent analysis suggests that ...
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PABPN1
Polyadenylate-binding protein 2 (PABP-2) also known as polyadenylate-binding nuclear protein 1 (PABPN1) is a protein that in humans is encoded by the ''PABPN1'' gene. PABN1 is a member of a larger family of poly(A)-binding proteins in the human genome. Function This gene encodes an abundant nuclear protein that binds with high affinity to nascent poly(A) tails. The protein is required for progressive and efficient polymerization of poly(A) tails on the 3' ends of eukaryotic genes and controls the size of the poly(A) tail to about 250 nt. At steady-state, this protein is localized in the nucleus whereas a different poly(A) binding protein is localized in the cytoplasm. An expansion of the trinucleotide (GCN) repeat from normal 10 to 11-17 at the 5' end of the coding region of this gene leads to autosomal dominant oculopharyngeal muscular dystrophy (OPMD) disease. Multiple splice variants have been described but their full-length nature is not known. One splice variant includes i ...
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Polynucleotide Adenylyltransferase
In enzymology, a polynucleotide adenylyltransferase () is an enzyme that catalyzes the chemical reaction :ATP + RNA-3'OH \rightleftharpoons pyrophosphate + RNApA-3'OH Thus, the two substrates of this enzyme are ATP and RNA, whereas its two products are pyrophosphate and RNA with an extra adenosine nucleotide at its 3' end. Human genes with this activity include TUT1, MTPAP, PAPOLA, PAPOLB, PAPOLG, TENT2, TENT4A, TENT4B, TENT5C, TENT5D. Naming This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing nucleotide groups (nucleotidyltransferases). The systematic name of this enzyme class is ATP:polynucleotide adenylyltransferase. Other names in common use include: * NTP polymerase * RNA adenylating enzyme * AMP polynucleotidylexotransferase * ATP-polynucleotide adenylyltransferase * ATP:polynucleotidylexotransferase * Poly(A) polymerase * Poly(A) synthetase * Polyadenylate nucleotidyltransferase * Polyadenylate polymerase ...
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Cleavage Stimulatory Factor
Cleavage stimulatory factor or cleavage stimulation factor (CstF or CStF) is a heterotrimeric protein, made up of the proteins CSTF1 (55kDa), CSTF2 (64kDa) and CSTF3 (77kDa), totalling about 200 kDa. It is involved in the cleavage of the 3' signaling region from a newly synthesized pre-messenger RNA (mRNA) molecule. CstF is recruited by cleavage and polyadenylation specificity factor (CPSF) and assembles into a protein complex on the 3' end to promote the synthesis of a functional polyadenine tail, which results in a mature mRNA molecule ready to be exported from the cell nucleus to the cytosol for translation. The amount of CstF in a cell is dependent on the phase of the cell cycle, increasing significantly during the transition from G0 phase to S phase in mouse fibroblast and human splenic B cells. Genes * CSTF1, CSTF2 or CSTF2T, CSTF3 Cleavage stimulation factor 77 kDa subunit is a protein that in humans is encoded by the ''CSTF3'' gene. The protein encoded by this gene is o ...
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X Chromosome Inactivation
X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into a transcriptionally inactive structure called heterochromatin. As nearly all female mammals have two X chromosomes, X-inactivation prevents them from having twice as many X chromosome gene products as males, who only possess a single copy of the X chromosome (see dosage compensation). The choice of which X chromosome will be inactivated in a particular embryonic cell is random in placental mammals such as humans, but once an X chromosome is inactivated it will remain inactive throughout the lifetime of the cell and its descendants in the organism (its cell line). The result is that the choice of inactivated X chromosome in all the cells of the organism is a random distribution, often with about half the cells having the paternal X chromosom ...
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Regulation Of Gene Expression
Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from Transcriptional regulation, transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network. Gene regulation is essential for viruses, prokaryotes and eukaryotes as it increases the versatility and adaptability of an organism by allowing the cell to express protein when needed. Although as early as 1951, Barbara McClintock showed interaction between two genetic loci, Activator (''Ac'') and Dissociator (''Ds''), in the color f ...
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