RNAi is antagonized by A→I hyper-editing

被引:108
作者
Scadden, ADJ [1 ]
Smith, CWJ [1 ]
机构
[1] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England
基金
英国惠康基金;
关键词
D O I
10.1093/embo-reports/kve244
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
RNA interference (RNAi) and adenosine to inosine conversion are both mechanisms that respond to double-stranded RNA (dsRNA) and have been suggested to have antiviral roles. RNAi involves processing of dsRNA to short interfering RNAs (siRNAs), which subsequently mediate degradation of the cognate mRNAs. Deamination of adenosines changes the coding capacity of the RNA, as inosine is decoded as guanosine, and alters the structure because A-U base pairs are replaced by I .U wobble pairs. Here we show that RNAi is inhibited if the triggering dsRNA is first deaminated by ADAR2. Moreover, we show that production of siRNAs is progressively inhibited with increasing deamination and that this is sufficient to explain the inhibition of RNAi upon hyper-editing of dsRNAs.
引用
收藏
页码:1107 / 1111
页数:5
相关论文
共 28 条
[11]  
HOUGH RF, 2000, RNA EDITING, P77
[12]   A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA [J].
Hutvágner, G ;
McLachlan, J ;
Pasquinelli, AE ;
Bálint, É ;
Tuschl, T ;
Zamore, PD .
SCIENCE, 2001, 293 (5531) :834-838
[13]   Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans [J].
Kamath, Ravi S. ;
Martinez-Campos, Maruxa ;
Zipperlen, Peder ;
Fraser, Andrew G. ;
Ahringer, Julie .
GENOME BIOLOGY, 2001, 2 (01)
[14]   A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans [J].
Knight, SW ;
Bass, BL .
SCIENCE, 2001, 293 (5538) :2269-2271
[15]   Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi [J].
Maeda, I ;
Kohara, Y ;
Yamamoto, M ;
Sugimoto, A .
CURRENT BIOLOGY, 2001, 11 (03) :171-176
[16]   On the wobble GoU and related pairs [J].
Masquida, B ;
Westhof, E .
RNA, 2000, 6 (01) :9-15
[17]   PURIFICATION AND PROPERTIES OF DOUBLE-STRANDED RNA-SPECIFIC ADENOSINE-DEAMINASE FROM CALF THYMUS [J].
OCONNELL, MA ;
KELLER, W .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (22) :10596-10600
[18]   EXPRESSION AND REGULATION BY INTERFERON OF A DOUBLE-STRANDED-RNA-SPECIFIC ADENOSINE-DEAMINASE FROM HUMAN-CELLS - EVIDENCE FOR 2 FORMS OF THE DEAMINASE [J].
PATTERSON, JB ;
SAMUEL, CE .
MOLECULAR AND CELLULAR BIOLOGY, 1995, 15 (10) :5376-5388
[19]  
PRESSMANSCHWART.S, 1992, P NATL ACAD SCI USA, V89, P11895
[20]   Protein-nucleic acid interactions and cellular responses to interferon [J].
Samuel, CE .
METHODS, 1998, 15 (03) :161-165