SiPools: Highly complex but accurately defined siRNA pools eliminate off-target effects

Nucleic Acids Research

Volumn 42, Issue 12, 2014, Pages 8049-8061

  Hannus, Michael ^a,b,c   Beitzinger, Michaela ^a,c   Engelmann, Julia C ^a   Weickert, Marie Theresa ^a   Spang, Rainer ^a   Hannus, Stefan ^b   Meister, Gunter ^a  

^a UNIVERSITY OF REGENSBURG   (Germany)

^b Intana Bioscience GmbH   (Germany)

^c SiTools Biotech GmbH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

MICRORNA; SMALL INTERFERING RNA; TRANSCRIPTOME;

ARTICLE; CONTROLLED STUDY; GENE EXPRESSION; GENE INACTIVATION; GENE SILENCING; GENE TARGETING; GENETIC TRANSFECTION; HUMAN; LIMIT OF DETECTION; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; RNA ANALYSIS; RNA GENE; RNA SEQUENCE; RNA STABILITY; RNA TRANSLATION; TNRC6A GENE; TNRC6B GENE; TNRC6C GENE;

HELA CELLS; HUMANS; INTERFERONS; MULTIGENE FAMILY; RNA INTERFERENCE; RNA, MESSENGER; RNA, SMALL INTERFERING;

EID: 84904013434     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gku480     Document Type: Article

References (61)

1. Dorsett, Y., Tuschl, T. (2004) siRNAs: applications in functional genomics and potential as therapeutics. Nat. Rev. Drug Discov., 3, 318-329.
2. Meister, G., Tuschl, T. (2004) Mechanisms of gene silencing by double-stranded RNA. Nature, 431, 343-349.
3. Siomi, H., Siomi, M.C. (2009) On the road to reading the RNA-interference code. Nature, 457, 396-404.
4. Iwasaki, S., Kobayashi, M., Yoda, M., Sakaguchi, Y., Katsuma, S., Suzuki, T., Tomari, Y. (2010) Hsc70/Hsp90 chaperone machinery mediates ATP-dependent RISC loading of small RNA duplexes. Mol. Cell, 39, 292-299.
5. Hammond, S.M., Boettcher, S., Caudy, A.A., Kobayashi, R., Hannon, G.J. (2001) Argonaute2, a link between genetic and biochemical analyses of RNAi. Science, 293, 1146-1150.
6. Johnston, M., Geoffroy, M.C., Sobala, A., Hay, R., Hutvagner, G. (2010) HSP90 protein stabilizes unloaded argonaute complexes and microscopic P-bodies in human cells. Mol. Biol. Cell, 21, 1462-1469.
7. Hutvagner, G., Simard, M.J. (2008) Argonaute proteins: key players in RNA silencing.Nat. Rev. Mol. Cell Biol., 9, 22-32.
8. Peters, L., Meister, G. (2007) Argonaute proteins: mediators of RNA silencing. Mol. Cell, 26, 611-623.
9. Ender, C., Meister, G. (2010) Argonaute proteins at a glance. J. Cell Sci., 123, 1819-1823.
10. Jinek, M., Doudna, J.A. (2009) A three-dimensional view of the molecular machinery of RNA interference. Nature, 457, 405-412.
11. Meister, G. (2013) Argonaute proteins: functional insights and emerging roles. Nat. Rev. Genet., 14, 447-459.
12. Meister, G., Landthaler, M., Patkaniowska, A., Dorsett, Y., Teng, G., Tuschl, T. (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol. Cell, 15, 185-197.
13. Liu, J., Carmell, M.A., Rivas, F.V., Marsden, C.G., Thomson, J.M., Song, J.J., Hammond, S.M., Joshua-Tor, L., Hannon, G.J. (2004) Argonaute2 is the catalytic engine of mammalian RNAi. Science, 305, 1437-1441.
14. Leuschner, P.J., Ameres, S.L., Kueng, S., Martinez, J. (2006) Cleavage of the siRNA passenger strand during RISC assembly in human cells. EMBO Rep., 7, 314-320.
15. Matranga, C., Tomari, Y., Shin, C., Bartel, D.P., Zamore, P.D. (2005) Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell, 123, 607-620.
16. Rand, T.A., Petersen, S., Du, F., Wang, X. (2005) Argonaute2 cleaves the anti-guide strand of siRNA during RISC activation. Cell, 123, 621-629.
17. Petri, S., Dueck, A., Lehmann, G., Putz, N., Rudel, S., Kremmer, E., Meister, G. (2011) Increased siRNA duplex stability correlates with reduced off-target and elevated on-target effects. RNA, 17, 737-749.
18. Gu, S., Jin, L., Zhang, F., Huang, Y., Grimm, D., Rossi, J.J., Kay, M.A. (2011) Thermodynamic stability of small hairpin RNAs highly influences the loading process of different mammalian Argonautes. Proc. Natl. Acad. Sci. U.S.A., 108, 9208-9213.
19. Wu, L., Fan, J., Belasco, J.G. (2008) Importance of translation and nonnucleolytic ago proteins for on-target RNA interference. Curr. Biol., 18, 1327-1332.
20. Jackson, A.L., Burchard, J., Schelter, J., Chau, B.N., Cleary, M., Lim, L., Linsley, P.S. (2006) Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complementarity. RNA, 12, 1179-1187.
21. Aleman, L.M., Doench, J., Sharp, P.A. (2007) Comparison of siRNA-induced off-target RNA and protein effects. RNA, 13, 385-395.
22. Bartel, D.P. (2009) MicroRNAs: target recognition and regulatory functions. Cell, 136, 215-233.
23. Carthew, R.W., Sontheimer, E.J. (2009) Origins and mechanisms of miRNAs and siRNAs. Cell, 136, 642-655.
24. Krol, J., Loedige, I., Filipowicz, W. (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat. Rev. Genet., 11, 597-610.
25. Huntzinger, E., Izaurralde, E. (2011) Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat. Rev. Genet., 12, 99-110.
26. Beitzinger, M., Peters, L., Zhu, J.Y., Kremmer, E., Meister, G. (2007) Identification of human microRNA targets from isolated Argonaute protein complexes. RNA Biol., 4, 76-84.
27. Weinmann, L., Hock, J., Ivacevic, T., Ohrt, T., Mutze, J., Schwille, P., Kremmer, E., Benes, V., Urlaub, H., Meister, G. (2009) Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs. Cell, 136, 496-507.
28. Rudel, S., Flatley, A., Weinmann, L., Kremmer, E., Meister, G. (2008) A multifunctional human Argonaute2-specific monoclonal antibody. RNA, 14, 1244-1253.
29. Pall, G.S., Hamilton, A.J. (2008) Improved northern blot method for enhanced detection of small RNA. Nat. Protoc., 3, 1077-1084.
30. Huber, W., von Heydebreck, A., Sultmann, H., Poustka, A., Vingron, M. (2002) Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics, 18(Suppl. 1), S96-S104.
31. Dai, M., Wang, P., Boyd, A.D., Kostov, G., Athey, B., Jones, E.G., Bunney, W.E., Myers, R.M., Speed, T.P., Akil, H. et al. (2005) Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Res., 33, e175.
32. Smyth, G.K. (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol., 3, 1544-6115.
33. Carvalho, B.S., Irizarry, R.A. (2010) A framework for oligonucleotide microarray preprocessing. Bioinformatics, 26, 2363-2367.
34. Wang, X., Terfve, C., Rose, J.C., Markowetz, F. (2011) HTSanalyzeR: an R/Bioconductor package for integrated network analysis of high-throughput screens. Bioinformatics, 27, 879-880.
35. Gentleman, R.C., Carey, V.J., Bates, D.M., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J. et al. (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol., 5, R80.
36. Sigoillot, F.D., Lyman, S., Huckins, J.F., Adamson, B., Chung, E., Quattrochi, B., King, R.W. (2012) A bioinformatics method identifies prominent off-targeted transcripts in RNAi screens. Nat. Methods, 9, 363-366.
37. Mayr, C., Hemann, M.T., Bartel, D.P. (2007) Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science, 315, 1576-1579.
38. Kittler, R., Heninger, A.K., Franke, K., Habermann, B., Buchholz, F. (2005) Production of endoribonuclease-prepared short interfering RNAs for gene silencing in mammalian cells. Nat. Methods, 2, 779-784.
39. Sigoillot, F.D., King, R.W. (2011) Vigilance and validation: keys to success in RNAi screening. ACS Chem. Biol., 6, 47-60.
40. Mohr, S., Bakal, C., Perrimon, N. (2010) Genomic screening with RNAi: results and challenges. Annu. Rev. Biochem., 79, 37-64.
41. Jackson, A.L., Linsley, P.S. (2010) Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application. Nat. Rev. Drug Discov., 9, 57-67.
42. Jackson, A.L., Burchard, J., Leake, D., Reynolds, A., Schelter, J., Guo, J., Johnson, J.M., Lim, L., Karpilow, J., Nichols, K. et al. (2006) Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing. RNA, 12, 1197-1205.
43. Elmen, J., Thonberg, H., Ljungberg, K., Frieden, M., Westergaard, M., Xu, Y., Wahren, B., Liang, Z., Orum, H., Koch, T. et al. (2005) Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. Nucleic Acids Res., 33, 439-447.
44. Ui-Tei, K., Naito, Y., Zenno, S., Nishi, K., Yamato, K., Takahashi, F., Juni, A., Saigo, K. (2008) Functional dissection of siRNA sequence by systematic DNA substitution: modified siRNA with a DNA seed arm is a powerful tool for mammalian gene silencing with significantly reduced off-target effect. Nucleic Acids Res., 36, 2136-2151.
45. Bramsen, J.B., Pakula, M.M., Hansen, T.B., Bus, C., Langkjaer, N., Odadzic, D., Smicius, R., Wengel, S.L., Chattopadhyaya, J., Engels, J.W. et al. (2010) A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects. Nucleic Acids Res., 38, 5761-5773.
46. Laursen, M.B., Pakula, M.M., Gao, S., Fluiter, K., Mook, O.R., Baas, F., Langklaer, N., Wengel, S.L., Wengel, J., Kjems, J. et al. (2010) Utilization of unlocked nucleic acid (UNA) to enhance siRNA performance in vitro and in vivo. Mol. Biosyst., 6, 862-870.
47. Betancur, J.G., Tomari, Y. (2012) Dicer is dispensable for asymmetric RISC loading in mammals. RNA, 18, 24-30.
48. Wu, H., Ma, H., Ye, C., Ramirez, D., Chen, S., Montoya, J., Shankar, P., Wang, X.A., Manjunath, N. (2011) Improved siRNA/shRNA functionality by mismatched duplex. PLoS ONE, 6, e28580.
49. Bramsen, J.B., Laursen, M.B., Damgaard, C.K., Lena, S.W., Babu, B.R., Wengel, J., Kjems, J. (2007) Improved silencing properties using small internally segmented interfering RNAs. Nucleic Acids Res., 35, 5886-5897.
50. Chen, P.Y., Weinmann, L., Gaidatzis, D., Pei, Y., Zavolan, M., Tuschl, T., Meister, G. (2008) Strand-specific 5'-O-methylation of siRNA duplexes controls guide strand selection and targeting specificity. RNA, 14, 263-274.
51. Peacock, H., Kannan, A., Beal, P.A., Burrows, C.J. (2011) Chemical modification of siRNA bases to probe and enhance RNA interference. J. Org. Chem., 76, 7295-7300.
52. Franceschini, A., Meier, R., Casanova, A., Kreibich, S., Daga, N., Andritschke, D., Dilling, S., Ramo, P., Emmenlauer, M., Kaufmann, A. et al. (2014) Specific inhibition of diverse pathogens in human cells by synthetic microRNA-like oligonucleotides inferred from RNAi screens. Proc. Natl. Acad. Sci. U.S.A., 111, 4548-4553.
53. Myers, J.W., Jones, J.T., Meyer, T., Ferrell, J.E. Jr. (2003) Recombinant Dicer efficiently converts large dsRNAs into siRNAs suitable for gene silencing. Nat. Biotechnol., 21, 324-328.
54. Myers, J.W., Chi, J.T., Gong, D., Schaner, M.E., Brown, P.O., Ferrell, J.E. (2006) Minimizing off-target effects by using diced siRNAs for RNA interference. J. RNAi Gene Silencing, 2, 181-194.
55. Kittler, R., Surendranath, V., Heninger, A.K., Slabicki, M., Theis, M., Putz, G., Franke, K., Caldarelli, A., Grabner, H., Kozak, K. et al. (2007) Genome-wide resources of endoribonuclease-prepared short interfering RNAs for specific loss-of-function studies. Nat. Methods, 4, 337-344.
56. Xiao, J., Feehery, C.E., Tzertzinis, G., Maina, C.V. (2009) E. coli RNase III(E38A) generates discrete-sized products from long dsRNA. RNA, 15, 984-991.
57. Rossi, J.J. (2006) RNAi as a treatment for HIV-1 infection. Biotechniques, 40, 25-29.
58. Rinn, J.L., Chang, H.Y. (2012) Genome regulation by long noncoding RNAs. Annu. Rev. Biochem., 81, 145-166.
59. Hombach, S., Kretz, M. (2013) The non-coding skin: exploring the roles of long non-coding RNAs in epidermal homeostasis and disease. Bioessays, 35, 1093-1100.
60. Gagnon, K.T., Li, L., Chu, Y., Janowski, B.A., Corey, D.R. (2014) RNAi factors are present and active in human cell nuclei. Cell Rep., 6, 211-221.
61. Robb, G.B., Brown, K.M., Khurana, J., Rana, T.M. (2005) Specific and potent RNAi in the nucleus of human cells. Nat. Struct. Mol. Biol., 12, 133-137.