Hypothesis: RNA editing of microRNA target sites in humans?

Adenosine (A) to inosine (I) RNA editing occurs widely in the human transcriptome, and a large proportion of editing sites are within untranslated regions (UTRs). MicroRNAs (miRNAs), an abundant class of regulatory genes, specify the expression of a large number of target genes by pairing to their 3' UTRs. To study the interplay between these two post-transcriptional events, we developed a computational pipeline to integrate sequence and miRNA tissue specificity data. The results show that some A-to-I RNA editing positions have a potential to block the miRNA:target recognition, although further computational simulation suggests that RNA editing tends to avoid miRNA target sites in general. We propose that a small proportion of RNA editing events may provide an additional layer of control on miRNA-mediated repression. Further investigation is needed to elucidate the functional effect of these special RNA editing events.

[1]  Anton J. Enright,et al.  RNA editing of human microRNAs , 2006, Genome Biology.

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

[3]  Alexander Rich,et al.  A-to-I RNA Editing: Recent News and Residual Mysteries* , 2003, The Journal of Biological Chemistry.

[4]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[5]  P. Seeburg,et al.  RNA editing of AMPA receptor subunit GluR-B: A base-paired intron-exon structure determines position and efficiency , 1993, Cell.

[6]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[7]  Brenda L Bass,et al.  RNA editing by adenosine deaminases that act on RNA. , 2002, Annual review of biochemistry.

[8]  Henry Mirsky,et al.  RNA editing of a miRNA precursor. , 2004, RNA.

[9]  T. Dawson,et al.  Regulation of alternative splicing by RNA editing , 1999, Nature.

[10]  Phillip D. Zamore,et al.  Ribo-gnome: The Big World of Small RNAs , 2005, Science.

[11]  D. Haussler,et al.  Aligning multiple genomic sequences with the threaded blockset aligner. , 2004, Genome research.

[12]  J. Castle,et al.  Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs , 2005, Nature.

[13]  C. Burge,et al.  Vertebrate MicroRNA Genes , 2003, Science.

[14]  Robert B. Russell,et al.  Principles of MicroRNATarget Recognition , 2005 .

[15]  N. Rajewsky microRNA target predictions in animals , 2006, Nature Genetics.

[16]  Eli Eisenberg,et al.  Letter from the editor: adenosine‐to‐inosine RNA editing in Alu repeats in the human genome , 2005, EMBO reports.

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

[18]  Alexander Rich,et al.  Widespread A-to-I RNA Editing of Alu-Containing mRNAs in the Human Transcriptome , 2004, PLoS biology.

[19]  D. Bartel,et al.  Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs , 2004, Nature Reviews Genetics.

[20]  C. Burge,et al.  Prediction of Mammalian MicroRNA Targets , 2003, Cell.

[21]  R. Emeson,et al.  Regulation of serotonin-2C receptor G-protein coupling by RNA editing , 1997, Nature.

[22]  C. Burge,et al.  The Widespread Impact of Mammalian MicroRNAs on mRNA Repression and Evolution , 2005, Science.

[23]  Sam Griffiths-Jones,et al.  The microRNA Registry , 2004, Nucleic Acids Res..

[24]  V. Ambros The functions of animal microRNAs , 2004, Nature.

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

[26]  Zipora Y. Fligelman,et al.  Systematic identification of abundant A-to-I editing sites in the human transcriptome , 2004, Nature Biotechnology.

[27]  R. Russell,et al.  Animal MicroRNAs Confer Robustness to Gene Expression and Have a Significant Impact on 3′UTR Evolution , 2005, Cell.