Evidence of off-target effects associated with long dsRNAs in Drosophila melanogaster cell-based assays

Nature Methods

Volumn 3, Issue 10, 2006, Pages 833-838

  Kulkarni, Meghana M ^a,b   Booker, Matthew ^a   Silver, Serena J ^a,d   Friedman, Adam ^a,b   Hong, Pengyu ^c   Perrimon, Norbert ^a,b   Mathey Prevot, Bernard ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^c BRANDEIS UNIVERSITY   (United States)

^d MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENTARY DNA; DOUBLE STRANDED RNA; ELONGATION FACTOR 1ALPHA; GREEN FLUORESCENT PROTEIN; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHOPROTEIN PHOSPHATASE 2A; RNA POLYMERASE II;

ARTICLE; CELL ASSAY; COMPUTER MODEL; CONTROLLED STUDY; CROSS HYBRIDIZATION; DNA MICROARRAY; DROSOPHILA MELANOGASTER; EVIDENCE BASED PRACTICE; FALSE POSITIVE RESULT; FREQUENCY ANALYSIS; GENETIC SCREENING; HIGH THROUGHPUT SCREENING; NONHUMAN; OPEN READING FRAME; PRACTICE GUIDELINE; PREDICTION; PRIORITY JOURNAL; QUALITY CONTROL; QUANTITATIVE ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA INTERFERENCE; RNA SEQUENCE; RNA TRANSCRIPTION; SENSITIVITY AND SPECIFICITY; SEQUENCE HOMOLOGY;

ANIMALS; DROSOPHILA MELANOGASTER; FALSE POSITIVE REACTIONS; GENE LIBRARY; GENETIC SCREENING; RNA INTERFERENCE; RNA, DOUBLE-STRANDED; SENSITIVITY AND SPECIFICITY;

DROSOPHILA MELANOGASTER;

EID: 33748994797     PISSN: 15487091     EISSN: 15491676     Source Type: Journal    
DOI: 10.1038/nmeth935     Document Type: Article

References (23)

1. Hannon, G.J. RNA interference. Nature 418, 244-251 (2002).
2. Jackson, A.L. et al. Expression profiling reveals off-target gene regulation by RNAi. Nat. Biotechnol. 21, 635-637 (2003).
3. Scacheri, P.C. et al. Short interfering RNAs can induce unexpected and divergent changes in the levels of untargeted proteins in mammalian cells. Proc. Natl. Acad Sci. USA 101, 1892-1897 (2004).
4. Birmingham, A. et al. 3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat. Methods 3, 199-204 (2006).
5. Doench, J.G. & Sharp, P.A. Specificity of microRNA target selection in translational repression. Genes Dev. 18, 504-511 (2004).
6. Echeverri, C.J. & Perrimon, N. High-throughput RNAi screening in cultured cells: A user's guide. Nat. Rev. Genet. 7, 373-384 (2006).
7. Elbashir, S.M., Lendeckel, W. & Tuschl, T. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 15, 188-200 (2001).
8. Qiu, S., Adema, C.M. & Lane, T.A computational study of off-target effects of RNA interference. Nucleic Acids Res. 33, 1834-1847 (2005).
9. Naito, Y. et al. dsCheck: Highly sensitive off-target search software for double-stranded RNA-mediated RNA interference. Nucleic Acids Res. 33, W589-W591 (2005).
10. Boutros, M. et al. Genome-wide RNAi analysis of growth and viability in Drosophila cells. Science 303, 832-835 (2004).
11. Flockhart, I. et al. FlyRNAi: The Drosophila RNAi screening center database. Nucleic Acids Res. 34, D489-D494 (2006).
12. Adams, M.D. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185-2195 (2000).
13. Hild, M. et al. An integrated gene annotation and transcriptional profiling approach towards the full gene content of the Drosophila genome. Genome Biol 5, R3 (2003).
14. Lin, X. et al. siRNA-mediated off-target gene silencing triggered by a 7 nt complementation. Nucleic Acids Res. 33, 4527-4535 (2005).
15. Wharton, K.A., Yedvobnick, B., Finnerty, V.G. & Artavanis-Tsakonas, S. opa: A novel family of transcribed repeats shared by the Notch locus and other developmentally regulated loci in D. melanogaster. Cell 40, 55-62 (1985).
16. Baeg, G.H., Zhou, R. & Perrimon, N. Genome-wide RNAi analysis of JAK/ STAT signaling components in Drosophila. Genes Dev. 19, 1861-1870 (2005).
17. Dasgupta, R. & Perrimon, N. Using RNAi to catch Drosophila genes in a web of interactions: Insights into cancer research. Oncogene 23, 8359-8365 (2004).
18. Nybakken, K., Vokes, S.A., Lin, T.Y., McMahon, A.P. & Perrimon, N. A genome-wide RNA interference screen in Drosophila melanogaster cells for new components of the Hh signaling pathway. Nat. Genet. 37, 1323-1332 (2005).
19. Arziman, Z., Horn, T. & Boutros, M. E-RNAi: A web application to design optimized RNAi constructs. Nucleic Acids Res. 33, W582-W588 (2005).
20. Gunsalus, K.C., Yueh, W.C., MacMenamin, P. & Piano, F. RNAiDB and PhenoBlast: Web tools for genome-wide phenotypic mapping projects. Nucleic Acids Res. 32 (Database issue), D406-D410 (2004).
21. Clemens, J.C. et al. Use of double-stranded RNA interference in Drosophila cell lines to dissect signal transduction pathways. Proc. Natl. Acad. Sci. USA 97, 6499-6503 (2000).
22. Friedman, A. & Perrimon, N. High-throughput approaches to dissecting MAPK signaling pathways. Methods published online 14 July 2006.
23. Benjamini, Y. & Yekutieli, D. Quantitative trait Loci analysis using the false discovery rate. Genetics 171, 783-790 (2005).