Disease relevance of Alu Elements

• Adenovirus type 2 preferentially stimulates polymerase III transcription of Alu elements by relieving repression: a potential role for chromatin [1].
• A deletion in an Alu repetitive sequence in the fifth intron of the c-sis gene of meningioma patients was previously described (M. Smidt et al., J. Clin. Invest., 86:1151-1157, 1990) [2].
• In this study, we report a large Finnish family in which an Alu element interferes with the coding region of the porphobilinogen deaminase (PBGD) gene resulting in acute intermittent porphyria (AIP) [3].
• In a screen for additional centromeric DNA sequences, four phage clones were obtained which contain alpha satellite as well as other sequences not usually found associated with tandemly repeated alpha satellite DNA, including L1 repetitive elements, an Alu element, and a novel AT-rich repeated sequence [4].
• Partially unspliced and fully spliced ELF3 mRNA, including a new Alu element in human breast cancer [5].

High impact information on Alu Elements

• We show that CCFDN is caused by a single-nucleotide substitution in an antisense Alu element in intron 6 of CTDP1 (encoding the protein phosphatase FCP1, an essential component of the eukaryotic transcription machinery), resulting in a rare mechanism of aberrant splicing and an Alu insertion in the processed mRNA [6].
• Between these two segments the human sex chromosomes differ by the insertion of an Alu element on the Y chromosome [7].
• Why then does RNA polymerase III transcribe the few 7SL genes so efficiently, while transcripts from the far more abundant Alu elements are not readily detectable [8]?
• We find that a human 7SL gene and a synthetic Alu sequence derived from it are expressed 50-100-fold more efficiently in vitro than either a representative Alu element or two 7SL pseudogenes [8].
• The sequences encoding the NGF receptor were molecularly cloned using the human Alu repetitive sequence as a probe [9].

Biological context of Alu Elements

• We suggest that the genomic sequences upstream from most Alu elements and 7SL pseudogenes do not contain this element, and consequently that only a small subset of such sequences can be transcribed in vivo [8].
• To begin to understand the molecular mechanisms leading to these rearrangements in mammalian cells, we developed an intron-based system to specifically induce chromosomal translocations at Alu elements, the most numerous family of repetitive elements in humans [10].
• (iv) The results of cell-free transcription experiments with Alu elements suggest that the in vitro transcription of Alu elements can be inhibited by 5'-CG-3' methylation [11].
• To identify DNA polymorphisms that are abundant in the human genome and are detectable by polymerase chain reaction amplification of genomic DNA, we tested the hypothesis that the polydeoxyadenylate tract of the Alu family of repetitive elements is polymorphic among human chromosomes [12].
• Plasmid clones containing a human Alu family repeat can be transcribed efficiently by RNA polymerase III in HeLa cell extract [13].

Associations of Alu Elements with chemical compounds

• Splice-mediated insertion of an Alu sequence inactivates ornithine delta-aminotransferase: a role for Alu elements in human mutation [14].
• Three Alu elements were identified in the platyrrhine and four in the prosimian DRB genes [15].
• Treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine rapidly decreased the level of H3-Lys9 methylation in the Alu elements, suggesting that H3-Lys9 methylation may be related to the suppression of Alu elements through DNA methylation [16].
• Search of common features usually implied in illegitimate recombination in mammalian cells revealed some association of these regions with palindromes, A + T-rich DNA segments, alternating purine/pyrimidine sequences and Alu family repeats [17].
• Rat prostatic steroid binding protein: characterisation of the Alu element upstream of the C3 genes [18].

Gene context of Alu Elements

• Genomic analyses revealed that the breaks were close to Alu elements in intron 16 of MORF and intron 2 of CBP and that duplications had occurred near the breakpoints [19].
• This function is carried out by the Alu domain, which consists of two proteins, SRP9 and SRP14, and the portion of SRP (7SL) RNA which is homologous to the Alu family of repetitive sequences [20].
• The recombination site in the GPA gene was confirmed to be within an Alu repetitive sequence [21].
• Unlike previously reported large germline deletions in BRCA1, neither breakpoint resides within an Alu element [22].
• A significant lack of Alu elements was observed across the major and minor breakpoint cluster regions of BCR and across a 25-kb region showing a high frequency of breakage in ABL1 [23].

Analytical, diagnostic and therapeutic context of Alu Elements

• PRINS harbors two Alu elements, it is transcribed by RNA polymerase II, and it is expressed at different levels in various human tissues [24].
• Sequence analysis of the deletions showed that the 5' breakpoints occurred at different sites in the same Alu element in intron 15, while the 3' breakpoints were located in different Alu repeats in intron 17 [25].
• Long-distance PCR amplified the genomic junction region, which involved the fusion of the 3' portion of an Alu element in intron 6 of MLL with the 5' portion of an Alu element in intron 7 of CBL [26].

References