3′UTR-located ALU Elements: Donors of Potetial miRNA Target Sites and Mediators of Network miRNA-based Regulatory Interactions

Recent research data reveal complex, network-based interactions between mobile elements and regulatory systems of eukaryotic cells. In this article, we focus on regulatory interactions between Alu elements and micro RNAs (miRNAs). Our results show that the majority of the Alu sequences inserted in 3′UTRs of analyzed human genes carry strong potential target sites for at least 53 different miRNAs. Thus, 3′UTR-located Alu elements may play the role of mobile regulatory modules that supply binding sites for miRNA regulation. Their abundance and ability to distribute a set of certain miRNA target sites may have an important role in establishment, extension, network organization, and, as we suppose – in the regulation and environment-dependent activation/inactivation of some elements of the miRNA regulatory system, as well as for a larger scale RNA-based regulatory interactions. The Alu-miRNA connection may be crucial especially for the primate/human evolution.

[1]  H. Kazazian.  Mobile Elements: Drivers of Genome Evolution , 2004, Science.

[2]  Jürgen Brosius,et al.  Waste not, want not--transcript excess in multicellular eukaryotes. , 2005, Trends in genetics : TIG.

[3]  A. Hatzigeorgiou,et al.  TarBase: A comprehensive database of experimentally supported animal microRNA targets. , 2005, RNA.

[4]  E. I. Rogaev,et al.  Small RNAs in Human Brain Development and Disorders , 2005, Biochemistry (Moscow).

[5]  K. Lindblad-Toh,et al.  Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals , 2005, Nature.

[6]  R. Sorek,et al.  Is abundant A-to-I RNA editing primate-specific? , 2004, Trends in genetics : TIG.

[7]  Hsien-Da Huang,et al.  miRNAMap: genomic maps of microRNA genes and their target genes in mammalian genomes , 2005, Nucleic Acids Res..

[8]  Kelvin Hsu,et al.  Monomeric scAlu and nascent dimeric Alu RNAs induced by adenovirus are assembled into SRP9/14-containing RNPs in HeLa cells. , 1996, Nucleic acids research.

[9]  J. Casacuberta,et al.  Plant LTR-retrotransposons and MITEs: control of transposition and impact on the evolution of plant genes and genomes. , 2003, Gene.

[10]  B. Cullen.  Transcription and processing of human microRNA precursors. , 2004, Molecular cell.

[11]  R. Russell,et al.  Principles of MicroRNA–Target Recognition , 2005, PLoS biology.

[12]  Brian J. Duistermars,et al.  Distinguishing humans from great apes with AluYb8 repeats. , 2004, Journal of molecular biology.

[13]  Phillip D Zamore,et al.  Sequence-Specific Inhibition of Small RNA Function , 2004, PLoS biology.

[14]  M. Batzer,et al.  From the margins of the genome: mobile elements shape primate evolution , 2005, BioEssays : news and reviews in molecular, cellular and developmental biology.

[15]  Ronald H. A. Plasterk,et al.  RNA Silencing: The Genome's Immune System , 2002, Science.

[16]  B. Panning,et al.  Activation of RNA polymerase III transcription of human Alu elements by herpes simplex virus. , 1994, Virology.

[17]  J. Brosius.  The Contribution of RNAs and Retroposition to Evolutionary Novelties , 2003, Genetica.

[18]  A transpositionally and transcriptionally competent Alu subfamily. , 1990, Molecular and cellular biology.

[19]  Vesselin Baev,et al.  MicroInspector: a web tool for detection of miRNA binding sites in an RNA sequence , 2005, Nucleic Acids Res..

[20]  J. Jurka,et al.  Repbase Update, a database of eukaryotic repetitive elements , 2005, Cytogenetic and Genome Research.

[21]  J. Mattick.  Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[22]  Stephen P. Fox,et al.  Lsh, an epigenetic guardian of repetitive elements. , 2004, Nucleic acids research.

[23]  M. G. Kidwell,et al.  PERSPECTIVE: TRANSPOSABLE ELEMENTS, PARASITIC DNA, AND GENOME EVOLUTION , 2001, Evolution; international journal of organic evolution.

[24]  S. Ryser,et al.  The SRP9/14 subunit of the human signal recognition particle binds to a variety of Alu-like RNAs and with higher affinity than its mouse homolog. , 1997, Nucleic acids research.

[25]  C. Gissi,et al.  Untranslated regions of mRNAs , 2002, Genome Biology.

[26]  T. Matise,et al.  Widespread RNA editing of embedded alu elements in the human transcriptome. , 2004, Genome research.

[27]  G. Dreyfuss,et al.  Numerous microRNPs in neuronal cells containing novel microRNAs. , 2003, RNA.

[28]  J. Mattick,et al.  Small regulatory RNAs in mammals. , 2005, Human molecular genetics.

[29]  J. Goodrich,et al.  The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock , 2004, Nature Structural &Molecular Biology.

[30]  P. Sharp,et al.  Embryonic stem cell-specific MicroRNAs. , 2003, Developmental cell.

[31]  A. Saïb,et al.  A Cellular MicroRNA Mediates Antiviral Defense in Human Cells , 2005, Science.

[32]  D. Mindell.  Fundamentals of molecular evolution , 1991 .

[33]  B. Cullen,et al.  Inhibition of a Yeast LTR Retrotransposon by Human APOBEC3 Cytidine Deaminases , 2005, Current Biology.

[34]  Deepak Grover,et al.  Nonrandom distribution of alu elements in genes of various functional categories: insight from analysis of human chromosomes 21 and 22. , 2003, Molecular biology and evolution.

[35]  George A Calin,et al.  MicroRNA fingerprints during human megakaryocytopoiesis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[36]  E. Triphosphat,et al.  FEBS Letters , 1987, FEBS Letters.

[37]  N. Rajewsky,et al.  Cell-type-specific signatures of microRNAs on target mRNA expression. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[38]  W. Makałowski,et al.  Genomic scrap yard: how genomes utilize all that junk. , 2000, Gene.

[39]  James A. Birchler,et al.  RNAi-mediated pathways in the nucleus , 2005, Nature Reviews Genetics.

[40]  Wen-Hsiung Li,et al.  Fundamentals of molecular evolution , 1990 .

[41]  D. Latchman,et al.  The human immunodeficiency virus tat protein increases the transcription of human Alu repeated sequences by increasing the activity of the cellular transcription factor TFIIIC. , 1992, Journal of Acquired Immune Deficiency Syndromes.

[42]  Stijn van Dongen,et al.  miRBase: microRNA sequences, targets and gene nomenclature , 2005, Nucleic Acids Res..

[43]  Shuang Huang,et al.  Involvement of MicroRNA in AU-Rich Element-Mediated mRNA Instability , 2005, Cell.

[44]  B. Howard,et al.  Modulation of HeLa cell growth by transfected 7SL RNA and Alu gene sequences. , 1991, Journal of Biological Chemistry.

[45]  J. Shapiro.  A 21st century view of evolution: genome system architecture, repetitive DNA, and natural genetic engineering. , 2005, Gene.

[46]  Vetle I. Torvik,et al.  Mammalian microRNAs derived from genomic repeats. , 2005, Trends in genetics : TIG.

[47]  M. Batzer,et al.  Alu repeats and human genomic diversity , 2002, Nature Reviews Genetics.

[48]  Jinchuan Xing,et al.  Alu element mutation spectra: molecular clocks and the effect of DNA methylation. , 2004, Journal of molecular biology.

[49]  J. Jurka.  Evolutionary impact of human Alu repetitive elements. , 2004, Current opinion in genetics & development.