7.4.

5 The Alu repeat occurs about once every 3 kb in the human genome and includes examples that are transcribed
The Alu repeat is the most abundant sequence in the human genome, with a copy number of about 1 000 000 (see Deininger, 1989; Smit, 1996). Alu repeats have a relatively high GC content and, although dispersed mainly throughout the euchromatic regions of the genome, have been reported to be preferentially located in R chromosome bands (Korenberg and Rykowski, 1988). The latter correspond to the pale bands seen when using standard Giemsa staining (see Box 2.4) and represent the most transcriptionally active regions of the genome. The full-length Alu repeat is about 280 bp long and is usually flanked by short (often 6 18 bp) direct repeats (i.e. the repeats are in the same orientation). The typical Alu sequence is a tandemly repeated dimer, with the repeats sharing an approximately 120 bp sequence followed by a short sequence which is rich in A residues on one strand and T residues on the complementary strand. However, there is asymmetry between the tandem repeats: one repeat unit contains an internal 32-bp sequence lacking in the other (Figure 7.18). Monomers, containing only one of the two tandem repeats, and various truncated versions of dimers and monomers are also common.

Figure 7.18 Structures of full-length Alu and LINE-1 repeats. The consensus standard Alu dimer is shown with two similar repeats terminating in an (A) n /(T) n like sequence. They have different sizes because of the insertion of a 32 bp element within the larger (more...) The two repeated units of the Alu sequence show a striking resemblance to the sequence for 7SL RNA, a component of the signal recognition particle, which facilitates transport of proteins across the membrane of the endoplasmic reticulum. Because of this and the observation of the Arich regions and the flanking direct repeats, it has been widely assumed that the Alu sequence has been propagated by retrotransposition from 7SL RNA, and therefore represents a processed 7SL RNA pseudogene (Figure 14.25). Certainly, transposition by Alu sequences is known to occur [presumably as a result of trans-acting cellular reverse transcriptases such as those encoded by LINE-1 (Kpn) elements (see below), and may occasionally cause clinical problems (Section 9.5.6)]. Possibly, the very high copy number achieved by this processed pseudogene is related to the presence of a promoter sequence in the 7SL RNA sequence (the 7SL RNA gene, like tRNA genes is transcribed by RNA polymerase III from an internal promoter, see Section 8.2.1). By contrast, processed pseudogenes from RNA polymerase II transcripts lack promoter sequences and their only chance of expression is if the integration event places them next to a functional promoter sequence. Currently, the function of the Alu sequence, if any, is unknown, although several roles have been considered (see Schmid, 1998). Although the average expected frequency is one copy per 3 kb, high density clustering of Alu repeats is known to occur in certain regions. Because of their ubiquity, Alu sequences have been considered to promote unequal recombination, a mechanism which while occasionally causing disease, may be evolutionarily advantageous in promoting

gene duplication (Section 9.3.2). Although conspicuously absent from coding sequences, Alu sequences are often found in noncoding intragenic locations, notably in introns and occasionally in untranslated sequences (see Figure 7.19). Consequently, they are often represented in the primary transcript RNA from genes encoding polypeptides, and occasionally in mRNA. The Alu sequence can also be transcribed from its internal promoter by RNA polymerase III in vitro, and in vivo transcription of some Alu sequences can result in the accumulation of a small cytoplasmic RNA which can be specifically bound by two cytoplasmic signal recognition particle proteins, SRP9 and SRP14