Developing microRNA screening as a functional genomics tool for disease research

Frontiers in Physiology

Volumn 4 AUG, Issue , 2013, Pages

  Lemons, Derek ^a,b   Maurya, Mano R ^a   Subramaniam, Shankar ^a   Mercola, Mark ^a,b  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^b BURNHAM INSTITUTE   (United States)

Author keywords

Functional genomics; Functional screens; MicroRNA target; Protein protein interaction; Proteomics; Systems biology and network biology

Indexed keywords

MICRORNA; SHORT HAIRPIN RNA; SMALL INTERFERING RNA;

ARTICLE; BIOGENESIS; CAENORHABDITIS ELEGANS; FUNCTIONAL GENOMICS; GENE OVEREXPRESSION; GENETIC SCREENING; HUMAN; IMMUNOPRECIPITATION; MEDICAL RESEARCH; NEOPLASM; NONHUMAN; PATHOGENESIS; PHENOTYPE; PROTEIN ANALYSIS; PROTEOMICS; RNA INTERFERENCE; TRANSCRIPTOMICS;

EID: 84884514267     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2013.00223     Document Type: Article

References (92)

1. Alexiou, P., Maragkakis, M., Papadopoulos, G. L., Reczko, M., and Hatzigeorgiou, A. G. (2009). Lost in translation: an assessment and perspective for computational microRNA target identification. Bioinformatics 25, 3049-3055. doi: 10.1093/bioinformatics/btp565
2. Alshalalfa, M., Bader, G. D., Goldenberg, A., Morris, Q., and Alhajj, R. (2012). Detecting microRNAs of high influence on protein functional interaction networks: a prostate cancer case study. BMC Syst. Biol. 6:112. doi: 10.1186/1752-0509-6-112
3. Alvarez-Saavedra, E., and Horvitz, H. R. (2010). Many families of C. elegans microRNAs are not essential for development or viability. Curr. Biol. 20, 367-373. doi: 10.1016/j.cub.2009.12.051
4. Arvey, A., Larsson, E., Sander, C., Leslie, C. S., and Marks, D. S. (2010). Target mRNA abundance dilutes microRNA and siRNA activity. Mol. Syst. Biol. 6, 363. doi: 10.1038/msb.2010.24
5. Baek, D., Villén, J., Shin, C., Camargo, F. D., Gygi, S. P., and Bartel, D. P. (2008). The impact of microRNAs on protein output. Nature 455, 64-71. doi: 10.1038/nature07242
6. Baigude, H., Ahsanullah Li, Z., Zhou, Y., and Rana, T. M. (2012). miR-TRAP: a benchtop chemical biology strategy to identify microRNA targets. Angew. Chem. Int. Ed. Engl. 51, 5880-5883. doi: 10.1002/anie.201201512
7. Bargaje, R., Gupta, S., Sarkeshik, A., Park, R., Xu, T., Sarkar, M., et al. (2012). Identification of novel targets for miR-29a using miRNA proteomics. PLoS ONE 7:e43243. doi: 10.1371/journal.pone.0043243
8. Bartel, D. P. (2009). MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233. doi: 10.1016/j.cell.2009.01.002
9. Becker, L. E., Lu, Z., Chen, W., Xiong, W., Kong, M., and Li, Y. (2012). A systematic screen reveals MicroRNA clusters that significantly regulate four major signaling pathways. PLoS ONE 7:e48474. doi: 10.1371/journal.pone.0048474
10. Beitzinger, M., Peters, L., Zhu, J. Y., Kremmer, E., and Meister, G. (2007). Identification of human microRNA targets from isolated argonaute protein complexes. RNA Biol. 4, 76-84. doi: 10.4161/rna.4.2.4640
11. Berns, K., Hijmans, E. M., Mullenders, J., Brummelkamp, T. R., Velds, A., Heimerikx, M., et al. (2004). A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature 428, 431-437. doi: 10.1038/nature02371
12. Birmingham, A., Anderson, E. M., Reynolds, A., Ilsley-Tyree, D., Leake, D., Fedorov, Y., et al. (2006). 3' UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat. Methods 3, 199-204. doi: 10.1038/nmeth854
13. Brennecke, J., Stark, A., Russell, R. B., and Cohen, S. M. (2005). Principles of microRNA-target recognition. PLoS Biol. 3:e85. doi: 10.1371/journal.pbio.0030085
14. Chang, K., Elledge, S. J., and Hannon, G. J. (2006). Lessons from Nature: microRNA-based shRNA libraries. Nat. Methods 3, 707-714. doi: 10.1038/nmeth923
15. Chen, Q.-R., Yu, L.-R., Tsang, P., Wei, J. S., Song, Y. K., Cheuk, A., et al. (2011). Systematic proteome analysis identifies transcription factor YY1 as a direct target of miR-34a. J. Proteome Res. 10, 479-487. doi: 10.1021/pr1006697
16. Chi, S. W., Zang, J. B., Mele, A., and Darnell, R. B. (2009). Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature 460, 479-486.
17. Chia, N.-Y., Chan, Y.-S., Feng, B., Lu, X., Orlov, Y. L., Moreau, D., et al. (2010). A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity. Nature 468, 316-320. doi: 10.1038/nature09531
18. Colas, A. R., McKeithan, W. L., Cunningham, T. J., Bushway, P. J., Garmire, L. X., Duester, G., et al. (2012). Whole-genome microRNA screening identifies let-7 and mir-18 as regulators of germ layer formation during early embryogenesis. Genes Dev. 26, 2567-2579. doi: 10.1101/gad.200758.112
19. Crews, C. M. (2010). Targeting the undruggable proteome: the small molecules of my dreams. Chem. Biol. 17, 551-555. doi: 10.1016/j.chembiol.2010.05.011
20. Cui, Q., Yu, Z., Purisima, E. O., and Wang, E. (2006). Principles of microRNA regulation of a human cellular signaling network. Mol. Syst. Biol. 2, 46. doi: 10.1038/msb4100089
21. Easow, G., Teleman, A. A., and Cohen, S. M. (2007). Isolation of microRNA targets by miRNP immunopurification. RNA 13, 1198-1204. doi: 10.1261/rna.563707
22. Elefant, N., Altuvia, Y., and Margalit, H. (2011). A wide repertoire of miRNA binding sites: prediction and functional implications. Bioinformatics 27, 3093-3101. doi: 10.1093/bioinformatics/btr534
23. Erler, J. T., and Linding, R. (2012). Network medicine strikes a blow against breast cancer. Cell 149, 731-733. doi: 10.1016/j.cell.2012.04.014
24. Eulalio, A., Mano, M., Ferro, M. D., Zentilin, L., Sinagra, G., Zacchigna, S., et al. (2012). Functional screening identifies miRNAs inducing cardiac regeneration. Nature 492, 376-381. doi: 10.1038/nature11739
25. Filipowicz, W., Bhattacharyya, S. N., and Sonenberg, N. (2008). Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat. Rev. Genet. 9, 102-114. doi: 10.1038/nrg2290
26. Friedman, R. C., Farh, K. K.-H., Burge, C. B., and Bartel, D. P. (2009). Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19, 92-105. doi: 10.1101/gr.082701.108
27. Garcia, D. M., Baek, D., Shin, C., Bell, G. W., Grimson, A., and Bartel, D. P. (2011). Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs. Nat. Struct. Mol. Biol. 18, 1139-1146. doi: 10.1038/nsmb.2115
28. Giraldez, A. J., Mishima, Y., Rihel, J., Grocock, R. J., Van Dongen, S., Inoue, K., et al. (2006). Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312, 75-79. doi: 10.1126/science.1122689
29. Grimson, A., Farh, K. K.-H., Johnston, W. K., Garrett-Engele, P., Lim, L. P., and Bartel, D. P. (2007). MicroRNA Targeting Specificity in Mammals: determinants beyond seed pairing. Mol. Cell 27, 91-105. doi: 10.1016/j.molcel.2007.06.017
30. Grueter, C. E., van Rooij, E., Johnson, B. A., DeLeon, S. M., Sutherland, L. B., Qi, X., et al. (2012). A cardiac microRNA governs systemic energy homeostasis by regulation of MED13. Cell 149, 671-683. doi: 10.1016/j.cell.2012.03.029
31. Guo, H., Ingolia, N. T., Weissman, J. S., and Bartel, D. P. (2010). Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466, 835-840. doi: 10.1038/nature09267
32. Hafner, M., Landthaler, M., Burger, L., Khorshid, M., Hausser, J., Berninger, P., et al. (2010). Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141, 129-141. doi: 10.1016/j.cell.2010.03.009
33. Helwak, A., Kudla, G., Dudnakova, T., and Tollervey, D. (2013). Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell 153, 654-665. doi: 10.1016/j.cell.2013.03.043
34. Hendrickson, D. G., Hogan, D. J., Herschlag, D., Ferrell, J. E., and Brown, P. O. (2008). Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. PLoS ONE 3:e2126. doi: 10.1371/journal.pone.0002126
35. Hendrickson, D. G., Hogan, D. J., McCullough, H. L., Myers, J. W., Herschlag, D., Ferrell, J. E., et al. (2009). Concordant regulation of translation and mRNA abundance for hundreds of targets of a human microRNA. PLoS Biol. 7:e1000238. doi: 10.1371/journal.pbio.1000238
36. Hernandez, P., Müller, M., and Appel, R. D. (2006). Automated protein identification by tandem mass spectrometry: issues and strategies. Mass Spectrom. Rev. 25, 235-254. doi: 10.1002/mas.20068
37. Ichimura, A., Ruike, Y., Terasawa, K., and Tsujimoto, G. (2011). miRNAs and regulation of cell signaling. FEBS J. 278, 1610-1618. doi: 10.1111/j.1742-4658.2011.08087.x
38. Jackson, A. L., Burchard, J., Leake, D., Reynolds, A., Schelter, J., Guo, J., et al. (2006). Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing. RNA 12, 1197-1205. doi: 10.1261/rna.30706
39. Jensen, O. N. (2004). Modification-specific proteomics: characterization of post-translational modifications by mass spectrometry. Curr. Opin. Chem. Biol. 8, 33-41. doi: 10.1016/j.cbpa.2003.12.009
40. Jentzsch, C., Leierseder, S., Loyer, X., Flohrschütz, I., Sassi, Y., Hartmann, D., et al. (2012). A phenotypic screen to identify hypertrophy-modulating microRNAs in primary cardiomyocytes. J. Mol. Cell. Cardiol. 52, 13-20. doi: 10.1016/j.yjmcc.2011.07.010
41. Johnson, D. S., Mortazavi, A., Myers, R. M., and Wold, B. (2007). Genome-wide mapping of in vivo protein-DNA interactions. Science 316, 1497-1502. doi: 10.1126/science.1141319
42. Kalsotra, A., Wang, K., Li, P.-F., and Cooper, T. A. (2010). MicroRNAs coordinate an alternative splicing network during mouse postnatal heart development. Genes Dev. 24, 653-658. doi: 10.1101/gad.1894310
43. Kaye, D. M., and Krum, H. (2007). Drug discovery for heart failure: a new era or the end of the pipeline? Nat. Rev. Drug Discov. 6, 127-139. doi: 10.1038/nrd2219
44. Keshava Prasad, T. S., Goel, R., Kandasamy, K., Keerthikumar, S., Kumar, S., Mathivanan, S., et al. (2009). Human protein reference database-2009 update. Nucleic Acids Res. 37, D767-D772. doi: 10.1093/nar/gkn892
45. Kim, N. H., Kim, H. S., Kim, N.-G., Lee, I., Choi, H.-S., Li, X.-Y., et al. (2011). p53 and microRNA-34 are suppressors of canonical Wnt signaling. Sci. Signal 4, ra71. doi: 10.1126/scisignal.2001744
46. Kishore, S., Jaskiewicz, L., Burger, L., Hausser, J., Khorshid, M., and Zavolan, M. (2011). A quantitative analysis of CLIP methods for identifying binding sites of RNA-binding proteins. Nat. Methods 8, 559-564. doi: 10.1038/nmeth.1608
47. Lagos-Quintana, M., Rauhut, R., Lendeckel, W., and Tuschl, T. (2001). Identification of novel genes coding for small expressed RNAs. Science 294, 853-858. doi: 10.1126/science.1064921
48. Le, M. T. N., Shyh-Chang, N., Khaw, S. L., Chin, L., Teh, C., Tay, J., et al. (2011). Conserved regulation of p53 network dosage by microRNA-125b occurs through evolving miRNA-target gene pairs. PLoS Genet. 7:e1002242. doi: 10.1371/journal.pgen.1002242
49. Lewis, B. P., Burge, C. B., and Bartel, D. P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20. doi: 10.1016/j.cell.2004.12.035
50. Lim, L. P., Lau, N. C., Garrett-Engele, P., Grimson, A., Schelter, J. M., Castle, J., et al. (2005). Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433, 769-773. doi: 10.1038/nature03315
51. Linsley, P. S., Schelter, J., Burchard, J., Kibukawa, M., Martin, M. M., Bartz, S. R., et al. (2007). Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression. Mol. Cell. Biol. 27, 2240-2252. doi: 10.1128/MCB.02005-06
52. Liu, H., Yue, D., Chen, Y., Gao, S.-J., and Huang, Y. (2010). Improving performance of mammalian microRNA target prediction. BMC Bioinformatics 11:476. doi: 10.1186/1471-2105-11-476
53. Liu, N., Bezprozvannaya, S., Williams, A. H., Qi, X., Richardson, J. A., Bassel-Duby, R., et al. (2008). microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes Dev. 22, 3242-3254. doi: 10.1101/gad.1738708
54. Marioni, J. C., Mason, C. E., Mane, S. M., Stephens, M., and Gilad, Y. (2008). RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res. 18, 1509-1517. doi: 10.1101/gr.079558.108
55. Mattoon, D. R., and Schweitzer, B. (2009). Profiling protein interaction networks with functional protein microarrays. Methods Mol. Biol. 563, 63-74. doi: 10.1007/978-1-60761-175-2_4
56. Melton, L. (2004). Protein arrays: proteomics in multiplex. Nature 429, 101-107. doi: 10.1038/429101a
57. Mercola, M., Colas, A., and Willems, E. (2013). Induced pluripotent stem cells in cardiovascular drug discovery. Circ. Res. 112, 534-548. doi: 10.1161/CIRCRESAHA.111.250266
58. Miska, E. A., Alvarez-Saavedra, E., Abbott, A. L., Lau, N. C., Hellman, A. B., McGonagle, S. M., et al. (2007). Most Caenorhabditis elegans microRNAs are individually not essential for development or viability. PLoS Genet. 3:e215. doi: 10.1371/journal.pgen.0030215
59. Moffat, J., Grueneberg, D. A., Yang, X., Kim, S. Y., Kloepfer, A. M., Hinkle, G., et al. (2006). A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 124, 1283-1298. doi: 10.1016/j.cell.2006.01.040
60. Nsair, A., and MacLellan, W. R. (2011). Induced pluripotent stem cells for regenerative cardiovascular therapies and biomedical discovery. Adv. Drug Deliv. Rev. 63, 324-330. doi: 10.1016/j.addr.2011.01.013
61. Overington, J. P., Al-Lazikani, B., and Hopkins, A. L. (2006). How many drug targets are there? Nat. Rev. Drug Discov. 5, 993-996. doi: 10.1038/nrd2199
62. Parsons, B. D., Schindler, A., Evans, D. H., and Foley, E. (2009). A direct phenotypic comparison of siRNA pools and multiple individual duplexes in a functional assay. PLoS ONE 4:e8471. doi: 10.1371/journal.pone.0008471
63. Poell, J. B., van Haastert, R. J., de Gunst, T., Schultz, I. J., Gommans, W. M., Verheul, M., et al. (2012). A functional screen identifies specific microRNAs capable of inhibiting human melanoma cell viability. PLoS ONE 7:e43569. doi: 10.1371/journal.pone.0043569
64. Rix, U., and Superti-Furga, G. (2009). Target profiling of small molecules by chemical proteomics. Nat. Chem. Biol. 5, 616-624. doi: 10.1038/nchembio.216
65. Sass, S., Dietmann, S., Burk, U. C., Brabletz, S., Lutter, D., Kowarsch, A., et al. (2011). MicroRNAs coordinately regulate protein complexes. BMC Syst. Biol. 5:136. doi: 10.1186/1752-0509-5-136
66. Schwarz, D. S., Hutvágner, G., Du, T., Xu, Z., Aronin, N., and Zamore, P. D. (2003). Asymmetry in the assembly of the RNAi enzyme complex. Cell 115, 199-208. doi: 10.1016/S0092-8674(03)00759-1
67. Selbach, M., Schwanhäusser, B., Thierfelder, N., Fang, Z., Khanin, R., and Rajewsky, N. (2008). Widespread changes in protein synthesis induced by microRNAs. Nature 455, 58-63. doi: 10.1038/nature07228
68. Shin, C., Nam, J.-W., Farh, K. K.-H., Chiang, H. R., Shkumatava, A., and Bartel, D. P. (2010). Expanding the MicroRNA Targeting Code: functional sites with centered pairing. Mol. Cell 38, 789-802. doi: 10.1016/j.molcel.2010.06.005
69. Shirdel, E. A., Xie, W., Mak, T. W., and Jurisica, I. (2011). NAViGaTing the micronome-using multiple microRNA prediction databases to identify signalling pathway-associated microRNAs. PLoS ONE 6:e17429. doi: 10.1371/journal.pone.0017429
70. Shreenivasaiah, P., Kim, D., and Wang, E. (2010). "microRNA regulation of networks of normal and cancer cells," in Cancer Systems Biology, ed E. Wang (Boca Raton, FL: CRC Press), 107-123.
71. Sims, D., Mendes-Pereira, A., Frankum, J., Burgess, D., Cerone, M.-A., Lombardelli, C., et al. (2011). High-throughput RNA interference screening using pooled shRNA libraries and next generation sequencing. Genome Biol. 12, R104. doi: 10.1186/gb-2011-12-10-r104
72. Small, E. M., O'Rourke, J. R., Moresi, V., Sutherland, L. B., McAnally, J., Gerard, R. D., et al. (2010). Regulation of PI3-kinase/Akt signaling by muscle-enriched microRNA-486. Proc. Natl. Acad. Sci. U.S.A. 107, 4218-4223. doi: 10.1073/pnas.1000300107
73. Stark, A., Brennecke, J., Bushati, N., Russell, R. B., and Cohen, S. M. (2005). Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution. Cell 123, 1133-1146. doi: 10.1016/j.cell.2005.11.023
74. Stockwell, B. R. (2000). Chemical genetics: ligand-based discovery of gene function. Nat. Rev. Genet. 1, 116-125. doi: 10.1038/35038557
75. Thum, T., Gross, C., Fiedler, J., Fischer, T., Kissler, S., Bussen, M., et al. (2008). MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 456, 980-984. doi: 10.1038/nature07511
76. Van Rooij, E., Sutherland, L. B., Qi, X., Richardson, J. A., Hill, J., and Olson, E. N. (2007). Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 316, 575-579. doi: 10.1126/science.1139089
77. Vinther, J., Hedegaard, M. M., Gardner, P. P., Andersen, J. S., and Arctander, P. (2006). Identification of miRNA targets with stable isotope labeling by amino acids in cell culture. Nucleic Acids Res. 34, e107. doi: 10.1093/nar/gkl590
78. Wang, K.-C., Garmire, L. X., Young, A., Nguyen, P., Trinh, A., Subramaniam, S., et al. (2010). Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth. Proc. Natl. Acad. Sci. U.S.A. 107, 3234-3239. doi: 10.1073/pnas.0914825107
79. Wang, X., and El Naqa, I. M. (2008). Prediction of both conserved and nonconserved microRNA targets in animals. Bioinformatics 24, 325-332. doi: 10.1093/bioinformatics/btm595
80. Wang, Z., Gerstein, M., and Snyder, M. (2009). RNA-Seq: a revolutionary tool for transcriptomics. Nat. Rev. Genet. 10, 57-63. doi: 10.1038/nrg2484
81. Wen, J., Parker, B. J., Jacobsen, A., and Krogh, A. (2011). MicroRNA transfection and AGO-bound CLIP-seq data sets reveal distinct determinants of miRNA action. RNA 17, 820-834. doi: 10.1261/rna.2387911
82. Whitehurst, A. W., Bodemann, B. O., Cardenas, J., Ferguson, D., Girard, L., Peyton, M., et al. (2007). Synthetic lethal screen identification of chemosensitizer loci in cancer cells. Nature 446, 815-819. doi: 10.1038/nature05697
83. Witkos, T., Koscianska, E., and Krzyzosiak, W. (2011). Practical aspects of microRNA target prediction. Curr. Mol. Med. 11, 93-109. doi: 10.2174/156652411794859250
84. Wu, C.-I., Shen, Y., and Tang, T. (2009). Evolution under canalization and the dual roles of microRNAs: a hypothesis. Genome Res. 19, 734-743. doi: 10.1101/gr.084640.108
85. Xia, W., Cao, G., and Shao, N. (2009). Progress in miRNA target prediction and identification. Sci. China C Life Sci. 52, 1123-1130. doi: 10.1007/s11427-009-0159-4
86. Yan, G.-R., Xu, S.-H., Tan, Z.-L., Liu, L., and He, Q.-Y. (2011). Global identification of miR-373-regulated genes in breast cancer by quantitative proteomics. Proteomics 11, 912-920. doi: 10.1002/pmic.201000539
87. Yang, Y., Chaerkady, R., Beer, M. A., Mendell, J. T., and Pandey, A. (2009). Identification of miR-21 targets in breast cancer cells using a quantitative proteomic approach. Proteomics 9, 1374-1384. doi: 10.1002/pmic.200800551
88. Yang, Y., Chaerkady, R., Kandasamy, K., Huang, T.-C., Selvan, L. D. N., Dwivedi, S. B., et al. (2010). Identifying targets of miR-143 using a SILAC-based proteomic approach. Mol. Biosyst. 6, 1873-1882. doi: 10.1039/c004401f
89. Zhang, L., Ding, L., Cheung, T. H., Dong, M.-Q., Chen, J., Sewell, A. K., et al. (2007). Systematic identification of C. elegans miRISC proteins, miRNAs, and mRNA targets by their interactions with GW182 proteins AIN-1 and AIN-2. Mol. Cell 28, 598-613. doi: 10.1016/j.molcel.2007.09.014
90. Zhao, Y., Ransom, J. F., Li, A., Vedantham, V., von Drehle, M., Muth, A. N., et al. (2007). Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell 129, 303-317. doi: 10.1016/j.cell.2007.03.030
91. Zhou, J., Wang, K.-C., Wu, W., Subramaniam, S., Shyy, J. Y.-J., Chiu, J.-J., et al. (2011). MicroRNA-21 targets peroxisome proliferators-activated receptor-alpha in an autoregulatory loop to modulate flow-induced endothelial inflammation. Proc. Natl. Acad. Sci. U.S.A. 108, 10355-10360. doi: 10.1073/pnas.1107052108
92. Zisoulis, D. G., Lovci, M. T., Wilbert, M. L., Hutt, K. R., Liang, T. Y., Pasquinelli, A. E., et al. (2010). Comprehensive discovery of endogenous Argonaute binding sites in Caenorhabditis elegans. Nat. Struct. Mol. Biol. 17, 173-179. doi: 10.1038/nsmb.1745