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Retrotransposition
A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transposition often results in duplication of the same genetic material. Barbara McClintock's discovery of them earned her a Nobel Prize in 1983. Its importance in personalized medicine is becoming increasingly relevant, as well as gaining more attention in data analytics given the difficulty of analysis in very high dimensional spaces. Transposable elements make up a large fraction of the genome and are responsible for much of the mass of DNA in a eukaryotic cell. Although TEs are selfish genetic elements, many are important in genome function and evolution. Transposons are also very useful to researchers as a means to alter DNA inside a living organism. There are at least two classes of TEs: Class I TEs or retrotransposons generally functio ...
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Short Interspersed Nuclear Element
Short interspersed nuclear elements (SINEs) are non-autonomous, non-coding transposable elements (TEs) that are about 100 to 700 base pairs in length. They are a class of retrotransposons, DNA elements that amplify themselves throughout eukaryotic genomes, often through RNA intermediates. SINEs compose about 13% of the mammalian genome. The internal regions of SINEs originate from tRNA and remain highly conserved, suggesting positive pressure to preserve structure and function of SINEs. While SINEs are present in many species of vertebrates and invertebrates, SINEs are often lineage specific, making them useful markers of divergent evolution between species. Copy number variation and mutations in the SINE sequence make it possible to construct phylogenies based on differences in SINEs between species. SINEs are also implicated in certain types of genetic disease in humans and other eukaryotes. In essence, short interspersed nuclear elements are genetic parasites which have evolv ...
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Composite Transposon
A composite transposon is similar in function to simple transposons and insertion sequence (IS) elements in that it has protein coding DNA segments flanked by inverted, repeated sequences that can be recognized by transposase enzymes. A composite transposon, however, is flanked by two separate IS elements which may or may not be exact replicas. Instead of each IS element moving separately, the entire length of DNA spanning from one IS element to the other is transposed as one complete unit. Composite transposons will also often carry one or more genes conferring antibiotic resistance. Flanked by SINEs in mammalian genomes Two SINEs may act in concert to flank and mobilize an intervening single copy DNA sequence. This was reported for a 710 bp DNA sequence upstream of the bovine beta globin gene. The DNA arrangement forms a composite transposon whose presence has been confirmed by the complete bovine genomic sequence where the mobilized sequence may be found on bovine chromosom ...
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Cold Spring Harbor Laboratory
Cold Spring Harbor Laboratory (CSHL) is a private, non-profit institution with research programs focusing on cancer, neuroscience, plant biology, genomics, and quantitative biology. It is one of 68 institutions supported by the Cancer Centers Program of the U.S. National Cancer Institute (NCI) and has been an NCI-designated Cancer Center since 1987. The Laboratory is one of a handful of institutions that played a central role in the development of molecular genetics and molecular biology. It has been home to eight scientists who have been awarded the Nobel Prize in Physiology or Medicine. CSHL is ranked among the leading basic research institutions in molecular biology and genetics with Thomson Reuters ranking it #1 in the world. CSHL was also ranked #1 in research output worldwide by ''Nature''. The Laboratory is led by Bruce Stillman, a biochemist and cancer researcher. Since its inception in 1890, the institution's campus on the North Shore of Long Island has also been ...
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Eukaryotic
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacteria and Archaea (both prokaryotes) make up the other two domains. The eukaryotes are usually now regarded as having emerged in the Archaea or as a sister of the Asgard archaea. This implies that there are only two domains of life, Bacteria and Archaea, with eukaryotes incorporated among archaea. Eukaryotes represent a small minority of the number of organisms, but, due to their generally much larger size, their collective global biomass is estimated to be about equal to that of prokaryotes. Eukaryotes emerged approximately 2.3–1.8 billion years ago, during the Proterozoic eon, likely as flagellated phagotrophs. Their name comes from the Greek εὖ (''eu'', "well" or "good") and κάρυον (''karyon'', "nut" or "kernel"). Euka ...
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Provirus
A provirus is a virus genome that is integrated into the DNA of a host cell. In the case of bacterial viruses (bacteriophages), proviruses are often referred to as prophages. However, proviruses are distinctly different from prophages and these terms should not be used interchangeably. Unlike prophages, proviruses do not excise themselves from the host genome when the host cell is stressed. This state can be a stage of virus replication, or a state that persists over longer periods of time as either inactive viral infections or an endogenous viral element. In inactive viral infections the virus will not replicate itself except through replication of its host cell. This state can last over many host cell generations. Endogenous retroviruses are always in the state of a provirus. When a (nonendogenous) retrovirus invades a cell, the RNA of the retrovirus is reverse-transcribed into DNA by reverse transcriptase, then inserted into the host genome by an integrase. A provirus does not ...
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RNA Polymerase III
In eukaryote cells, RNA polymerase III (also called Pol III) is a protein that transcribes DNA to synthesize ribosomal 5S rRNA, tRNA and other small RNAs. The genes transcribed by RNA Pol III fall in the category of "housekeeping" genes whose expression is required in all cell types and most environmental conditions. Therefore, the regulation of Pol III transcription is primarily tied to the regulation of cell growth and the cell cycle, thus requiring fewer regulatory proteins than RNA polymerase II. Under stress conditions however, the protein Maf1 represses Pol III activity. Rapamycin is another Pol III inhibitor via its direct target TOR. Transcription The process of transcription (by any polymerase) involves three main stages: *Initiation, requiring construction of the RNA polymerase complex on the gene's promoter *Elongation, the synthesis of the RNA transcript *Termination, the finishing of RNA transcription and disassembly of the RNA polymerase complex Initiation In ...
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RNA Polymerase II
RNA polymerase II (RNAP II and Pol II) is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of eukaryotic cells. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase. A wide range of transcription factors are required for it to bind to upstream gene promoters and begin transcription. Discovery Early studies suggested a minimum of two RNAPs: one which synthesized rRNA in the nucleolus, and one which synthesized other RNA in the nucleoplasm, part of the nucleus but outside the nucleolus. In 1969, science experimentalists Robert Roeder and William Rutter definitively discovered an additional RNAP that was responsible for transcription of some kind of RNA in the nucleoplasm. The finding was obtained by the use of ion-exchange chromatography via DEAE coated Sephadex beads. The technique separated the enzymes ...
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LINEs
Line most often refers to: * Line (geometry), object with zero thickness and curvature that stretches to infinity * Telephone line, a single-user circuit on a telephone communication system Line, lines, The Line, or LINE may also refer to: Arts, entertainment, and media Films * ''Lines'' (film), a 2016 Greek film * ''The Line'' (2017 film) * ''The Line'' (2009 film) * ''The Line'', a 2009 independent film by Nancy Schwartzman Podcasts * ''The Line'' (podcast), 2021 by Dan Taberski Literature * Line (comics), a term to describe a subset of comic book series by a publisher * ''Line'' (play), by Israel Horovitz, 1967 * Line (poetry), the fundamental unit of poetic composition * "Lines" (poem), an 1837 poem by Emily Brontë * ''The Line'' (memoir), by Arch and Martin Flanagan * ''The Line'' (play), by Timberlake Wertenbaker, 2009 Music Albums * ''Lines'' (The Walker Brothers album), 1976 * ''Lines'' (Pandelis Karayorgis album), 1995 * ''Lines'' (Unthanks album), 201 ...
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Long Terminal Repeat
A long terminal repeat (LTR) is a pair of identical sequences of DNA, several hundred base pairs long, which occur in eukaryotic genomes on either end of a series of genes or pseudogenes that form a retrotransposon or an endogenous retrovirus or a retroviral provirus. All retroviral genomes are flanked by LTRs, while there are some retrotransposons without LTRs. Typically, an element flanked by a pair of LTRs will encode a reverse transcriptase and an integrase, allowing the element to be copied and inserted at a different location of the genome. Copies of such an LTR-flanked element can often be found hundreds or thousands of times in a genome. LTR retrotransposons comprise about 8% of the human genome. The first LTR sequences were found by A.P. Czernilofsky and J. Shine in 1977 and 1980. Transcription The LTR-flanked sequences are partially transcribed into an RNA intermediate, followed by reverse transcription into complementary DNA (cDNA) and ultimately dsDNA (double-stra ...
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Retrovirus
A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus ''retro'' (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Although retroviruses have different subfamilies, they have three basic groups: the oncoretroviruses (oncogenic retroviruses), the lentiviruses (slow retroviruses) and the spumaviruses (foamy viruses). The oncoretroviruses are able to cause cancer in some species, the lentiviru ...
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Reverse Transcriptase
A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, by retrotransposon mobile genetic elements to proliferate within the host genome, and by eukaryotic cells to extend the telomeres at the ends of their linear chromosomes. Contrary to a widely held belief, the process does not violate the flows of genetic information as described by the classical central dogma, as transfers of information from RNA to DNA are explicitly held possible. Retroviral RT has three sequential biochemical activities: RNA-dependent DNA polymerase activity, ribonuclease H (RNase H), and DNA-dependent DNA polymerase activity. Collectively, these activities enable the enzyme to convert single-stranded RNA into double-stranded cDNA. In retroviruses and retrotransposons, this cDNA can then integrate into the host genom ...
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CDNA
In genetics, complementary DNA (cDNA) is DNA synthesized from a single-stranded RNA (e.g., messenger RNA (mRNA) or microRNA (miRNA)) template in a reaction catalyzed by the enzyme reverse transcriptase. cDNA is often used to express a specific protein in a cell that does not normally express that protein (i.e., heterologous expression), or to sequence or quantify mRNA molecules using DNA based methods (qPCR, RNA-seq). cDNA that codes for a specific protein can be transferred to a recipient cell for expression, often bacterial or yeast expression systems. cDNA is also generated to analyze transcriptomic profiles in bulk tissue, single cells, or single nuclei in assays such as microarrays, qPCR, and RNA-seq. cDNA is also produced naturally by retroviruses (such as HIV-1, HIV-2, simian immunodeficiency virus, etc.) and then integrated into the host's genome, where it creates a provirus. The term ''cDNA'' is also used, typically in a bioinformatics context, to refer to an mR ...
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