Editing independent effects of ADARs on the miRNA/siRNA pathways

被引:154
作者
Heale, Bret S. E. [1 ]
Keegan, Liam P. [1 ]
McGurk, Leeanne [1 ]
Michlewski, Gracjan [1 ]
Brindle, James [1 ]
Stanton, Chloe M. [1 ]
Caceres, Javier F. [1 ]
O'Connell, Mary A. [1 ]
机构
[1] Western Gen Hosp, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
基金
英国医学研究理事会;
关键词
Drosophila; DSH1; microprocessor; RNA editing; RNA interference; DOUBLE-STRANDED-RNA; DYSCHROMATOSIS SYMMETRICA HEREDITARIA; ADENOSINE-DEAMINASE; MESSENGER-RNA; GENE; BINDING; DROSOPHILA; MUTATIONS; INTERFERON; EXPRESSION;
D O I
10.1038/emboj.2009.244
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Adenosine deaminases acting on RNA (ADARs) are best known for altering the coding sequences of mRNA through RNA editing, as in the GluR-B Q/R site. ADARs have also been shown to affect RNA interference (RNAi) and microRNA processing by deamination of specific adenosines to inosine. Here, we show that ADAR proteins can affect RNA processing independently of their enzymatic activity. We show that ADAR2 can modulate the processing of mir-376a2 independently of catalytic RNA editing activity. In addition, in a Drosophila assay for RNAi deaminase-inactive ADAR1 inhibits RNAi through the siRNA pathway. These results imply that ADAR1 and ADAR2 have biological functions as RNA-binding proteins that extend beyond editing per se and that even genomically encoded ADARs that are catalytically inactive may have such functions. The EMBO Journal (2009) 28, 3145-3156. doi:10.1038/sj.emboj.2009.244; Published online 27 August 2009
引用
收藏
页码:3145 / 3156
页数:12
相关论文
共 55 条
[1]   RNA hyperediting and alternative splicing of hematopoietic cell phosphatase (PTPN6) gene in acute myeloid leukemia [J].
Beghini, A ;
Ripamonti, CB ;
Peterlongo, P ;
Roversi, G ;
Cairoli, R ;
Morra, E ;
Larizza, L .
HUMAN MOLECULAR GENETICS, 2000, 9 (15) :2297-2304
[2]   RNA editing of human microRNAs [J].
Blow, Matthew J. ;
Grocock, Russell J. ;
van Dongen, Stijn ;
Enright, Anton J. ;
Dicks, Ed ;
Futreal, P. Andrew ;
Wooster, Richard ;
Stratton, Michael R. .
GENOME BIOLOGY, 2006, 7 (04)
[3]   Down-regulation of RNA editing in pediatric astrocytomas - ADAR2 editing activity inhibits cell migration and proliferation [J].
Cenci, Caterina ;
Barzotti, Rita ;
Galeano, Federica ;
Corbelli, Sandro ;
Rota, Rossella ;
Massimi, Luca ;
Di Rocco, Concezio ;
O'Connell, Mary A. ;
Gallo, Angela .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (11) :7251-7260
[4]   Disruption of murine Tenr results in teratospermia and male infertility [J].
Connolly, CM ;
Dearth, AT ;
Braun, RE .
DEVELOPMENTAL BIOLOGY, 2005, 278 (01) :13-21
[5]   Dynamic association of RNA-editing enzymes with the nucleolus [J].
Desterro, JMP ;
Keegan, LR ;
Lafarga, M ;
Berciano, MT ;
O'Connell, M ;
Carmo-Fonseca, M .
JOURNAL OF CELL SCIENCE, 2003, 116 (09) :1805-1818
[6]   Characterization of the 5′-flanking region of the human RNA-specific adenosine deaminase ADAR1 gene and identification of an interferon-inducible ADAR1 promoter [J].
George, CX ;
Samuel, CE .
GENE, 1999, 229 (1-2) :203-213
[7]   The Microprocessor complex mediates the genesis of microRNAs [J].
Gregory, RI ;
Yan, KP ;
Amuthan, G ;
Chendrimada, T ;
Doratotaj, B ;
Cooch, N ;
Shiekhattar, R .
NATURE, 2004, 432 (7014) :235-240
[8]   The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a [J].
Guil, Sonia ;
Caceres, Javier F. .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2007, 14 (07) :591-596
[9]   Liver disintegration in the mouse embryo caused by deficiency in the RNA-editing enzyme ADAR1 [J].
Hartner, JC ;
Schmittwolf, C ;
Kispert, A ;
Müller, AM ;
Higuchi, M ;
Seeburg, PH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (06) :4894-4902
[10]   Interferon-α stimulation of liver cells enhances hepatitis delta virus RNA editing in early infection [J].
Hartwig, D ;
Schoeneich, L ;
Greeve, J ;
Schütte, C ;
Dorn, I ;
Kirchner, H ;
Hennig, H .
JOURNAL OF HEPATOLOGY, 2004, 41 (04) :667-672