alu elements


Summary: The Alu sequence family (named for the restriction endonuclease cleavage enzyme Alu I) is the most highly repeated interspersed repeat element in humans (over a million copies). It is derived from the 7SL RNA component of the SIGNAL RECOGNITION PARTICLE and contains an RNA polymerase III promoter. Transposition of this element into coding and regulatory regions of genes is responsible for many heritable diseases.

Top Publications

  1. Salih F, Salih B, Kogan S, Trifonov E. Epigenetic nucleosomes: Alu sequences and CG as nucleosome positioning element. J Biomol Struct Dyn. 2008;26:9-16 pubmed
    ..Thus, Alu sequences may harbor special epigenetic nucleosomes with methylation-dependent regulatory functions. Nucleosome DNA sequence probe is suggested to detect locations of such regulatory nucleosomes in the sequences. ..
  2. Abrusan G, Giordano J, Warburton P. Analysis of transposon interruptions suggests selection for L1 elements on the X chromosome. PLoS Genet. 2008;4:e1000172 pubmed publisher
    ..elements on the X chromosome is due to their function in X inactivation, and that the accumulation of Alu elements near genes is adaptive...
  3. Corvelo A, Eyras E. Exon creation and establishment in human genes. Genome Biol. 2008;9:R141 pubmed publisher
    A large proportion of species-specific exons are alternatively spliced. In primates, Alu elements play a crucial role in the process of exon creation but many new exons have appeared through other mechanisms...
  4. Aleshin A, Zhi D. Recombination-associated sequence homogenization of neighboring Alu elements: signature of nonallelic gene conversion. Mol Biol Evol. 2010;27:2300-11 pubmed publisher
    ..We believe that these observations help to illuminate the nature and impact of the enigmatic phenomenon of gene conversion. ..
  5. Volff J, Brosius J. Modern genomes with retro-look: retrotransposed elements, retroposition and the origin of new genes. Genome Dyn. 2007;3:175-90 pubmed publisher
    ..Therefore, the 'retro-look' of genomes is in fact indicative of their modernity. ..
  6. Chen L, Carmichael G. Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: functional role of a nuclear noncoding RNA. Mol Cell. 2009;35:467-78 pubmed publisher
    ..Taken together, these results assign a biological function to a large noncoding nuclear RNA in the regulation of mRNA export...
  7. Subramanyam M, Diez Roux A, Pilsner J, Villamor E, Donohue K, Liu Y, et al. Social factors and leukocyte DNA methylation of repetitive sequences: the multi-ethnic study of atherosclerosis. PLoS ONE. 2013;8:e54018 pubmed publisher
  8. Pandey R, Mukerji M. From 'JUNK' to just unexplored noncoding knowledge: the case of transcribed Alus. Brief Funct Genomics. 2011;10:294-311 pubmed publisher
    ..Dynamic and functional Alu repeats seem to be centrally placed to modulate the transcriptional landscape of human genome. ..
  9. Zhang W, Edwards A, Fan W, Deininger P, Zhang K. Alu distribution and mutation types of cancer genes. BMC Genomics. 2011;12:157 pubmed publisher
    b>Alu elements are the most abundant retrotransposable elements comprising ~11% of the human genome...

More Information


  1. Hormozdiari F, Alkan C, Ventura M, Hajirasouliha I, Malig M, Hach F, et al. Alu repeat discovery and characterization within human genomes. Genome Res. 2011;21:840-9 pubmed publisher
    ..69%). Using these data, we develop an experimental and computational screen to identify ancestry informative Alu retrotransposition events among different human populations. ..
  2. Resta N, Giorda R, Bagnulo R, Beri S, Della Mina E, Stella A, et al. Breakpoint determination of 15 large deletions in Peutz-Jeghers subjects. Hum Genet. 2010;128:373-82 pubmed publisher
    ..Of the 30 breakpoints, 16 were located in Alu elements, revealing non-allelic homologous recombination (NAHR) as the putative mechanism for the deletions of the STK11 ..
  3. Gómez Pérez L, Alfonso Sanchez M, Perez Miranda A, Garcia Obregon S, Builes J, Bravo M, et al. Genetic admixture estimates by Alu elements in Afro-Colombian and Mestizo populations from Antioquia, Colombia. Ann Hum Biol. 2010;37:488-500 pubmed publisher
    ..The usefulness of the Alu elements as Ancestry Informative Markers (AIMs) was evaluated through differences in weighted allelic frequencies (delta ..
  4. Marullo M, Zuccato C, Mariotti C, Lahiri N, Tabrizi S, Di Donato S, et al. Expressed Alu repeats as a novel, reliable tool for normalization of real-time quantitative RT-PCR data. Genome Biol. 2010;11:R9 pubmed publisher
    ..This result is particularly important for clinical diagnosis and biomarker validation studies based on mRNA detection in human blood. ..
  5. Baccarelli A, Wright R, Bollati V, Tarantini L, Litonjua A, Suh H, et al. Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med. 2009;179:572-8 pubmed publisher
    ..12). We found decreased repeated-element methylation after exposure to traffic particles. Whether decreased methylation mediates exposure-related health effects remains to be determined. ..
  6. de Smith A, Walters R, Coin L, Steinfeld I, Yakhini Z, Sladek R, et al. Small deletion variants have stable breakpoints commonly associated with alu elements. PLoS ONE. 2008;3:e3104 pubmed publisher
  7. Bach D, Peddi S, Mangeat B, Lakkaraju A, Strub K, Trono D. Characterization of APOBEC3G binding to 7SL RNA. Retrovirology. 2008;5:54 pubmed publisher
    ..We thus conclude that 7SL RNA is not an essential mediator of the virion packaging of these antiviral cytidine deaminases. ..
  8. Abdurashitov M, Tomilov V, Chernukhin V, Degtyarev S. A physical map of human Alu repeats cleavage by restriction endonucleases. BMC Genomics. 2008;9:305 pubmed publisher
    ..Alu repeats digestions provide the main contribution to the patterns of human chromosomal DNA cleavage. This corresponds to the experimental data on total human DNA hydrolysis with restriction enzymes. ..
  9. Hasler J, Samuelsson T, Strub K. Useful 'junk': Alu RNAs in the human transcriptome. Cell Mol Life Sci. 2007;64:1793-800 pubmed
    b>Alu elements are the most abundant repetitive elements in the human genome; they have amplified by retrotransposition to reach the present number of more than one million copies...
  10. Krull M, Petrusma M, Makalowski W, BROSIUS J, Schmitz J. Functional persistence of exonized mammalian-wide interspersed repeat elements (MIRs). Genome Res. 2007;17:1139-45 pubmed
  11. Jepson J, Reenan R. RNA editing in regulating gene expression in the brain. Biochim Biophys Acta. 2008;1779:459-70 pubmed
    ..ADARs have recently been revealed to have a novel role in the primate lineage: the widespread editing of Alu elements, which comprise approximately 10% of the human genome...
  12. Mariner P, Walters R, Espinoza C, Drullinger L, Wagner S, Kugel J, et al. Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Mol Cell. 2008;29:499-509 pubmed publisher
    ..These studies provide an explanation for why mouse cells harbor two major classes of SINEs, whereas human cells contain only one. ..
  13. Ram O, Schwartz S, Ast G. Multifactorial interplay controls the splicing profile of Alu-derived exons. Mol Cell Biol. 2008;28:3513-25 pubmed publisher
    Exonization of Alu elements creates primate-specific genomic diversity. Here we combine bioinformatic and experimental methodologies to reconstruct the molecular changes leading to exon selection...
  14. Weibrecht I, Gavrilović M, Lindbom L, Landegren U, Wählby C, Söderberg O. Visualising individual sequence-specific protein-DNA interactions in situ. N Biotechnol. 2012;29:589-98 pubmed publisher
    ..Although efficiency of detection currently is limiting, we conclude that in situ PLA can be used to achieve a highly selective analysis of PDIs in single cells. ..
  15. Churakov G, Grundmann N, Kuritzin A, BROSIUS J, Makałowski W, Schmitz J. A novel web-based TinT application and the chronology of the Primate Alu retroposon activity. BMC Evol Biol. 2010;10:376 pubmed publisher
  16. Igarashi S, Suzuki H, Niinuma T, Shimizu H, Nojima M, Iwaki H, et al. A novel correlation between LINE-1 hypomethylation and the malignancy of gastrointestinal stromal tumors. Clin Cancer Res. 2010;16:5114-23 pubmed publisher
    ..Hypomethylation may increase the malignant potential of GISTs by inducing accumulation of chromosomal aberrations. ..
  17. Cardelli M. Alu PCR. Methods Mol Biol. 2011;687:221-9 pubmed publisher
    ..The resulting -complex electrophoretic pattern may show sample-to-sample variability due to insertion, deletion, or sequence change of Alu retrotransposons, or caused by length variation of the sequence interposed between two Alus. ..
  18. Sela N, Mersch B, Gal Mark N, Lev Maor G, Hotz Wagenblatt A, Ast G. Comparative analysis of transposed element insertion within human and mouse genomes reveals Alu's unique role in shaping the human transcriptome. Genome Biol. 2007;8:R127 pubmed
    ..Our findings reveal many effects of TEs on these two transcriptomes. These effects are substantially greater in human than in mouse, which is due to the presence of Alu elements in human.
  19. Xiang S, Liu Z, Zhang B, Zhou J, Zhu B, Ji J, et al. Methylation status of individual CpG sites within Alu elements in the human genome and Alu hypomethylation in gastric carcinomas. BMC Cancer. 2010;10:44 pubmed publisher
    ..However, the maintenance and methylation status of each CpG site within Alu elements (Alu) and its methylation status have not well characterized...
  20. Kimmel M, Mathaes M. Modeling neutral evolution of Alu elements using a branching process. BMC Genomics. 2010;11 Suppl 1:S11 pubmed publisher
    b>Alu elements occupy about eleven percent of the human genome and are still growing in copy numbers...
  21. Roman Gomez J, Jimenez Velasco A, Agirre X, Castillejo J, Navarro G, San Jose Eneriz E, et al. Repetitive DNA hypomethylation in the advanced phase of chronic myeloid leukemia. Leuk Res. 2008;32:487-90 pubmed
    ..Furthermore, a more profound level of hypomethylation was observed among BC samples compared with CP samples. Our data suggest that repetitive DNA hypomethylation are closely associated with CML progression. ..
  22. Han K, Lee J, Meyer T, Wang J, Sen S, Srikanta D, et al. Alu recombination-mediated structural deletions in the chimpanzee genome. PLoS Genet. 2007;3:1939-49 pubmed
    With more than 1.2 million copies, Alu elements are one of the most important sources of structural variation in primate genomes...
  23. Kitkumthorn N, Keelawat S, Rattanatanyong P, Mutirangura A. LINE-1 and Alu methylation patterns in lymph node metastases of head and neck cancers. Asian Pac J Cancer Prev. 2012;13:4469-75 pubmed
    The potential use of hypomethylation of Long INterspersed Element 1 (LINE-1) and Alu elements (Alu) as a biomarker has been comprehensively assessed in several cancers, including head and neck squamous cell carcinoma (HNSCC)...
  24. Levy A, Schwartz S, Ast G. Large-scale discovery of insertion hotspots and preferential integration sites of human transposed elements. Nucleic Acids Res. 2010;38:1515-30 pubmed publisher
    ..In particular, retrotransposed Alu elements contain a non-canonical single nucleotide hotspot for insertion of other Alu sequences...
  25. Udaka T, Okamoto N, Aramaki M, Torii C, Kosaki R, Hosokai N, et al. An Alu retrotransposition-mediated deletion of CHD7 in a patient with CHARGE syndrome. Am J Med Genet A. 2007;143A:721-6 pubmed
    ..As demonstrated in this study, MP/LC is a promising method for characterizing exonic deletions, which are largely left unexamined in most routine mutation analysis. ..
  26. Pal A, Srivastava T, Sharma M, Mehndiratta M, Das P, Sinha S, et al. Aberrant methylation and associated transcriptional mobilization of Alu elements contributes to genomic instability in hypoxia. J Cell Mol Med. 2010;14:2646-54 pubmed publisher
    ..This might be a cause of genetic heterogeneity in tumours especially in variegated hypoxic environment and lead to a development of foci of more aggressive tumour cells. ..
  27. Umylny B, Presting G, Efird J, Klimovitsky B, Ward W. Most human Alu and murine B1 repeats are unique. J Cell Biochem. 2007;102:110-21 pubmed
    ..We examined all Alu elements over 200 nucleotides and all B1 elements over 100 nucleotides in the human and mouse genomes, and analyzed the ..
  28. Li J, Levanon E, Yoon J, Aach J, Xie B, Leproust E, et al. Genome-wide identification of human RNA editing sites by parallel DNA capturing and sequencing. Science. 2009;324:1210-3 pubmed publisher
    ..This efficient approach greatly expands the repertoire of RNA editing targets and can be applied to studies involving RNA editing-related human diseases. ..
  29. Xing J, Zhang Y, Han K, Salem A, Sen S, Huff C, et al. Mobile elements create structural variation: analysis of a complete human genome. Genome Res. 2009;19:1516-26 pubmed publisher
  30. Pandey R, Mandal A, Jha V, Mukerji M. Heat shock factor binding in Alu repeats expands its involvement in stress through an antisense mechanism. Genome Biol. 2011;12:R117 pubmed publisher
    ..This presence underlies an antisense-mediated mechanism that represents a novel component of Alu and HSF involvement in the heat shock response. ..
  31. Burns K, Boeke J. Human transposon tectonics. Cell. 2012;149:740-52 pubmed publisher
    ..Key questions going forward include how and how much new transposition events affect human health and disease. ..
  32. Hancks D, Kazazian H. Active human retrotransposons: variation and disease. Curr Opin Genet Dev. 2012;22:191-203 pubmed publisher
    ..Finally we discuss studies that provide insights into the past and current activity of these retrotransposons, and shed light on not just when, but where, retrotransposition occurs and its part in genetic variation. ..
  33. Chen L, Carmichael G. Gene regulation by SINES and inosines: biological consequences of A-to-I editing of Alu element inverted repeats. Cell Cycle. 2008;7:3294-301 pubmed
    The Alu elements are conserved approximately 300 nucleotide long repeat sequences that belong to the SINE family of retrotransposons found abundantly in primate genomes...
  34. Rodriguez J, Vives L, Jorda M, Morales C, Muñoz M, Vendrell E, et al. Genome-wide tracking of unmethylated DNA Alu repeats in normal and cancer cells. Nucleic Acids Res. 2008;36:770-84 pubmed
    ..Demethylation of Alu elements occurs in aging and cancer processes and has been associated with gene reactivation and genomic instability...
  35. Ray D, Xing J, Salem A, Batzer M. SINEs of a nearly perfect character. Syst Biol. 2006;55:928-35 pubmed
  36. Hogg M, Paro S, Keegan L, O Connell M. RNA editing by mammalian ADARs. Adv Genet. 2011;73:87-120 pubmed publisher
    ..Lack of editing by ADARs has been implicated in disorders such as forebrain ischemia and Amyotrophic Lateral Sclerosis (ALS) and this will also be discussed. ..
  37. Schumann G. APOBEC3 proteins: major players in intracellular defence against LINE-1-mediated retrotransposition. Biochem Soc Trans. 2007;35:637-42 pubmed
  38. Nakkuntod J, Avihingsanon Y, Mutirangura A, Hirankarn N. Hypomethylation of LINE-1 but not Alu in lymphocyte subsets of systemic lupus erythematosus patients. Clin Chim Acta. 2011;412:1457-61 pubmed publisher
    ..We examined and compared the methylation levels of long interspersed nuclear element 1s (LINE-1) and Alu elements in normal and SLE CD4+ T lymphocytes, CD8+ T lymphocytes and B lymphocytes by the combined bisulfite ..
  39. Deininger P. Alu elements: know the SINEs. Genome Biol. 2011;12:236 pubmed publisher
    b>Alu elements are primate-specific repeats and comprise 11% of the human genome. They have wide-ranging influences on gene expression. Their contribution to genome evolution, gene regulation and disease is reviewed.
  40. Antonaki A, Demetriades C, Polyzos A, Banos A, Vatsellas G, Lavigne M, et al. Genomic analysis reveals a novel nuclear factor-?B (NF-?B)-binding site in Alu-repetitive elements. J Biol Chem. 2011;286:38768-82 pubmed publisher
  41. Carmi S, Borukhov I, Levanon E. Identification of widespread ultra-edited human RNAs. PLoS Genet. 2011;7:e1002317 pubmed publisher
    ..Ultra-edited RNAs exhibit the known sequence motif of ADARs and tend to localize in sense strand Alu elements. Compared to sites of mild editing, ultra-editing occurs primarily in Alu-rich regions, where potential base ..
  42. Iskow R, McCabe M, Mills R, Torene S, Pittard W, Neuwald A, et al. Natural mutagenesis of human genomes by endogenous retrotransposons. Cell. 2010;141:1253-61 pubmed publisher
    ..Our data indicate that transposon-mediated mutagenesis is extensive in human genomes and is likely to have a major impact on human biology and diseases. ..
  43. Osenberg S, Paz Yaacov N, Safran M, Moshkovitz S, Shtrichman R, Sherf O, et al. Alu sequences in undifferentiated human embryonic stem cells display high levels of A-to-I RNA editing. PLoS ONE. 2010;5:e11173 pubmed publisher
    ..regions but the majority is found in non-coding regions, such as 3'UTRs, 5'UTRs and introns - mainly in Alu elements. While editing is found in all tissues, the highest levels of editing are found in the brain...
  44. Tanaka Y, Yamashita R, Suzuki Y, Nakai K. Effects of Alu elements on global nucleosome positioning in the human genome. BMC Genomics. 2010;11:309 pubmed publisher
    ..After masking Alu elements, these periodicities were greatly diminished...
  45. Xie H, Wang M, Bonaldo M, Rajaram V, Stellpflug W, Smith C, et al. Epigenomic analysis of Alu repeats in human ependymomas. Proc Natl Acad Sci U S A. 2010;107:6952-7 pubmed publisher
    ..bisulfite sequencing approach that simultaneously generates methylation profiles for thousands of Alu elements and their flanking sequences...
  46. Tsirigos A, Rigoutsos I. Alu and b1 repeats have been selectively retained in the upstream and intronic regions of genes of specific functional classes. PLoS Comput Biol. 2009;5:e1000610 pubmed publisher
  47. Gu T, Yi X, Zhao X, Zhao Y, Yin J. Alu-directed transcriptional regulation of some novel miRNAs. BMC Genomics. 2009;10:563 pubmed publisher
    ..a variety of Alu-related sequences from multiple sources were pooled and filtered to obtain a subset containing Alu elements and characterized miRNA genes for which there is clear evidence of full-length transcription (embedded in EST)...
  48. Saito Y, Suzuki H, Tsugawa H, Nakagawa I, Matsuzaki J, Kanai Y, et al. Chromatin remodeling at Alu repeats by epigenetic treatment activates silenced microRNA-512-5p with downregulation of Mcl-1 in human gastric cancer cells. Oncogene. 2009;28:2738-44 pubmed publisher
  49. Richards K, Zhang B, Baggerly K, Colella S, Lang J, Schuller D, et al. Genome-wide hypomethylation in head and neck cancer is more pronounced in HPV-negative tumors and is associated with genomic instability. PLoS ONE. 2009;4:e4941 pubmed publisher
    ..Global hypomethylation was variable in HNSCC. Its correlation with both HPV status and degree of LOH as a surrogate for genomic instability may reflect alternative oncogenic pathways in HPV-positive versus HPV-negative tumors. ..
  50. Zilberman D, Safran M, Paz N, Amariglio N, Simon A, Fridman E, et al. Does RNA editing play a role in the development of urinary bladder cancer?. Urol Oncol. 2011;29:21-6 pubmed publisher
    ..editing sites in RNA encoding for proteins (BLCAP, Cyfip2, FLNA, GluB Q/R) as well as in RNA transcribed from Alu elements in noncoding regions of the genes encoding for CARD11, FANCC, MDM4, BRCA1, and RBBP9 proteins...
  51. Kim P, Lam H, Urban A, Korbel J, Affourtit J, Grubert F, et al. Analysis of copy number variants and segmental duplications in the human genome: Evidence for a change in the process of formation in recent evolutionary history. Genome Res. 2008;18:1865-74 pubmed publisher
    ..b>Alu elements, a major class of genomic repeats, had previously been identified as prime drivers of SD formation...
  52. Gal Mark N, Schwartz S, Ast G. Alternative splicing of Alu exons--two arms are better than one. Nucleic Acids Res. 2008;36:2012-23 pubmed publisher
    ..They are composed of two related but distinct monomers, left and right arms. Intronic Alu elements may acquire mutations that generate functional splice sites, a process called exonization...
  53. Mattick J, Mehler M. RNA editing, DNA recoding and the evolution of human cognition. Trends Neurosci. 2008;31:227-33 pubmed publisher
    ..We suggest that the predominance of Alu elements in the human genome is the result of their evolutionary co-adaptation as a modular substrate for RNA editing, ..