Most recent AluY insertions in human gene introns reduce the content of the primary transcripts in a cell type specific manner Yuri B. Lebedev ⁎ ,1 , Anna L. Amosova 1 , Ilgar Z. Mamedov, Gleb Y. Fisunov, Eugene D. Sverdlov Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Moscow, Russia Received 16 June 2006; received in revised form 19 September 2006; accepted 28 September 2006 Received by M. Batzer Available online 17 October 2006 Abstract Being the most effectively transposed primate-specific SINEs, Alu elements are present in more than one million copies in the human genome and include most recently transposed subsets of AluY elements that are polymorphic in humans. Although Alu elements are commonly thought to play an essential role in shaping and functioning of primate genomes, the understanding of the impact of recent Alu insertions on human gene expression is far from being comprehensive. Here we compared hnRNA contents for allele pairs of genes heterozygous for AluY insertions in their introns in human cell lines of various origins. We demonstrated that some AluY insertions correlated with decreased content of the corresponding hnRNAs. The effect observed does not depend on sequences of Alu elements and their orientation but is likely to be cell type specific. © 2006 Elsevier B.V. All rights reserved. Keywords: Human retroelements; Alu repeats; Alu polymorphism; Transcription of human gene alleles; Human cell lines 1. Introduction Alu elements are the most abundant class of primate-specific SINE retroposons that have reached over 1 million copies in the human genome (Lander et al., 2001; Hedges and Batzer, 2005). Saturation of ancestral genomes with Alu elements have started approximately 60 mya and continued in the course of primate evolution with different rates of amplification to form several distinct families (Batzer and Deininger, 2002). While a majority of Alu elements belonging to ‘old’ AluJ and AluS families have arisen in ancestral genomes 48–35 mya and have been inactivated by random mutations (reviewed in Kapitonov and Jurka, 1996; Rowold and Herrera, 2000), several ‘master’ genes of AluY family were being transposed even after the divergence of hominid and chimpanzee lineages (Cordaux et al., 2004). More than half of roughly 5000 insertions of human specific AluY elements are thought to be dimorphic in humans (Salem et al., 2003). High copy numbers in the genome, some preference of GC- reach regions by young elements, and long co-habitation of Alu elements with host genomes suggest their significant role in primate genome evolution. Alu elements might affect evolution of genes and their function by a wide variety of mechanisms. Recent studies support the involvement of Alu elements in proteome diversity through alternative splicing (Lev-Maor et al., 2003), genome shaping through segmental duplications (Bailey et al., 2003), retroposition-mediated deletions (Haya- kawa et al., 2001), and postintegration recombinations (Salem et al., 2003). Some of these events lead to human gene inactivation and have been reported to be associated with genetic diseases (observed in Deininger and Batzer, 1999). Although the number of observations in favor of Alus' influence on human genome evolution is constantly growing, the understanding of the impact of recent Alu insertions on genome functioning is far from being comprehensive. One of the possible approaches to study the effect of Alu elements on gene expression could be a comparison of expression levels of two alleles differing in that one of them contains an intronic Alu insertion, whereas the other does not. In this approach, the Gene 390 (2007) 122 – 129 www.elsevier.com/locate/gene Abbreviations: RE(s), Retroelements; SINE(s), Short Interspersed Elements; LINE(s), Long Interspersed Elements; hnRNA, heterogeneous nuclear RNA: a primary transcript; mya, millions years ago. ⁎ Corresponding author. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, Moscow 117997, Russia. Tel.: +7 495 330 4288; fax: +7 495 330 6538. E-mail address: lebedev_yb@ibch.ru (Y.B. Lebedev). 1 These authors contributed equally to this work. 0378-1119/$ - see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.gene.2006.09.031