Alu Mania

I’ve been talking about Alu elements for weeks now, so I was going to try to change the topic.  But alas, I can’t stop myself.  Here is some more Alu Fun for those similarly intrigued by the manner in which these nifty reformatting devices can facilitate evolution.

First, here is a decent video that outlines the basics of Alu retrotansposition.

Second, remember how it has become clear that the genome has a three-dimensional architecture?

Well, our little reformatting devices have the ability to alter genomic structure:

Alu sequences are interspersed throughout the genomes of primate cells, occurring singly and in clusters around RNA polymerase II-transcribed genes. Because these repeat elements are capable of positioning nucleosomes in in vitro reconstitutes, we investigated whether they also  influence in vivo chromatin structure. When assayed collectively using consensus sequence probes and native chromatin as template, Alu family members were found to confer rotational positioning on nucleosomes or nucleosome-like particles. In particular, a 10-base pair pattern of DNase I nicking that spanned the RNA polymerase III box A promoter motif extended upstream to cover diverse 5′-flanking sequences, suggesting that Alu repeats may influence patterns of nucleosome formation over neighboring regions. Computational analysis of a set of naturally occurring Alu sequences indicated that nucleosome positioning information is intrinsic to these elements. Inasmuch as local chromatin organization influences gene expression, the capacity of Alu sequences to affect chromatin structure as demonstrated here may help to clarify some features of these elements.

And finally, yet another transcription factor binding site is housed in the Alu element:

The negative calcium response element type 2 (nCARE) is a regulatory DNA sequence consisting of a palindromic core sequence and several upstream T residues, which was originally described in the 5′ flank of the human PTH [parathyroid hormone – MG] gene. The nCARE functions in an orientation-specific manner to inhibit PTH transcription in response to raised extracellular calcium levels. Here we report that the PTH nCARE lies within a hitherto unrecognized ALU-like element situated approximately 3.6 kB upstream of the human PTH gene transcriptional start site. Since ALU elements are repetitive DNA sequences, which are widely distributed throughout the human genome, we hypothesized that other nCARE elements might also exist. A search of the GenBank/EMBL databases with the nCARE core sequence confirmed this to be the case showing the presence of 111 copies of the nCARE in human/primate sequences. Analysis of the 7SL RNA sequence from which ALU elements derive also showed the presence of an nCARE “core” sequence immediately upstream of the polyA+ tail. These data suggest that the nCARE is derived from retrotransposition of 7SL RNA and forms an integral part of many ALU elements; reverse transcription of the poly-A+ tail of 7SL RNA adds T residues, which on retrotransposition into genomic DNA with the core sequence, forms an ALU element containing a functional nCARE. Some of the genes associated with nCARE elements express products which are affected by extracellular calcium concentrations and work is in progress to determine the functional effects of nCARE at these sites. The widespread distribution of the nCARE throughout the genome, however, raises the possibility that this may be a common mechanism by which extracellular calcium regulates gene transcription.

Good stuff.

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