Alu repeats

Alu sequence is a short stretch of DNA originally characterized by the action of the Alu restriction endonuclease. Alu sequences of different kinds occur in large numbers in primate genomes. In fact, Alu sequences are the most abundant mobile elements in the human genome. They are derived from the small cytoplasmic 7SL RNA, a component of the signal recognition particle. The event, when a copy of the 7SL RNA became a precursor of the Alu sequence, took place in the genome of an ancestor of Supraprimates. Transcript The bulk of human genome contains many sequence that do not code for any protein. These regions of genome are sometimes referred to as "junk" Dna,and make up more than 98% pf human genome.Included in the non-coding dna are many repetitive dna sequences. Two important families of repetitive elements are LINEs(Long Interspersed Elements) and the SINEs(Short Interspersed Elements).L1 is the most prevalent LINEs, and makes up about 17% of human genome. Alu is the most prevalent SINEs,and equals about 11% of the genome,Alu and other SINEs are "defective" transposons;they depend on the enzymes of other transposons like L1,for mobility.It is estimated that there are about 75000 L1 and 1200000 Alu elements distributed throughout the human genome. Lets take a closer look at a single copy of each L1 ,at approximately 20 times the length of Alu,encodes all the molecular machinery needed to replicate and move within the genome.An l1 element is approximately 6000 nucleotides in length, with two untranslated regions(UTRs)and two open reading frames(ORFs). The ORF protein products assemble into complex that enables L1 and elements such as Alu to move throughout the genome.The structure of L1 is a stark contrast with that of the tiny 300 nucleotide Alu,Alu elements have no open reading frames and so encode no proteins. Alu elements are characterized by a sequence with two G/C rich regions: the let(L-Alu) and the right(R-Alu) monomers. An A-rich linker connects these monomers. Alu elements end with a poly-A tail.In the genome, Alu elements are immediately flanked by A=T rich sequences. The L-Alu regions contains two specific features Box A and Box B,which are binding sites of transcription factors and RNA polymerase III.Alu elements are transcribed into RNA by these proteins until they reach a stretch of T's is the genomic DNA. The Alu Rna can act as template for the formation of a new Alu element that can itself in a new genome location. A likely model for this process requires the enzyme, a reverse transcriptase(rt),encoded by L1. In addition to reverse transcription,L1 rt has teh unique ability to nick DNA in a site-preferential manner. Most ofen the nick is made at the consensus sequence TTAAA.This can create a single-stranded sequences of Ts that hydrogen bonds with the poly-A tail of the Alu RNA to form a short RNA/DNA heteroduplex. The heteroduplex than can serve as a primer for L1 rt to synthesize a complementary (c) DNA strand. A second nick is mode on the opposite strand, a variable distance from the initial cleavage site. Then, either the L1 rt or a cellular Dna polymerase synthesizes the second DNA strand. This results in an Alu element inserted into a novel position of the genome. The insertion also creates a direct repeat sequence on either side of the element.

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Channels: Genetics Molecular Genetics

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Uploaded by: ( Send Message ) on 07-07-2009. Dnatube suggest users to have interest in drug testing, mesothelioma, insurance, medical lawyers.

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