ABB  Vol.5 No.4 , March 2014
Using Engineered microRNAs as Vectors for Animal RNA Interference: Promises and Challenges
ABSTRACT

microRNAs are post-transcriptional regulators of gene expression that recruit RNA silencing complexes to target transcripts to prevent translation and promote their degradation. Experimental studies suggest that microRNA binding to target transcripts can result in as much as a 90% decrease in gene expression. Because of this feature, the microRNA pathway has been utilized as a vehicle for potent RNA interference (RNAi). In recent years, significant advances have been made in engineering artificial microRNA vectors for RNAi in a number of biological systems, with the most progress in plants but also some success in mouse and human cell lines. In this mini-review, we provide a brief discussion of the potential of this technology in comparison with other RNAi strategies, and the current challenges in the design of microRNA-based RNAi vectors, particularly for animal systems.


Cite this paper
Chen, J. and Zeller, R. (2014) Using Engineered microRNAs as Vectors for Animal RNA Interference: Promises and Challenges. Advances in Bioscience and Biotechnology, 5, 301-310. doi: 10.4236/abb.2014.54037.
References
[1]   Lu, J., Getz, G., Miska, E.A., Alvarez-Saavedra, E., Lamb, J., et al. (2005) MicroRNA Expression Profiles Classify Human Cancers. Nature, 435, 834-838. http://dx.doi.org/10.1038/nature03702

[2]   Calin, G.A. and Croce, C.M. (2006) MicroRNA-Cancer Connection: The Beginning of a New Tale. Cancer Research, 66, 7390-7394. http://dx.doi.org/10.1158/0008-5472.CAN-06-0800

[3]   Bartel, D.P. (2009) MicroRNAs: Target Recognition and Regulatory Functions. Cell, 136, 215-233.
http://dx.doi.org/10.1016/j.cell.2009.01.002

[4]   Lee, R.C., Feinbaum, R.L. and Ambros, V. (1993) The C. elegans Heterochronic Gene Lin-4 Encodes Small RNAs with Antisense Complementarity to Lin-14. Cell, 75, 843-854. http://dx.doi.org/10.1016/0092-8674(93)90529-Y

[5]   Wightman, B., Ha, I. and Ruvkun, G. (1993) Posttranscriptional Regulation of the Heterochronic Gene Lin-14 by Lin-4 Mediates Temporal Pattern Formation in C. elegans. Cell, 75, 855-862.
http://dx.doi.org/10.1016/0092-8674(93)90530-4

[6]   Ha, I., Wightman, B. and Ruvkun, G. (1996) A Bulged Lin-4/Lin-14 RNA Duplex Is Sufficient for Caenorhabditis elegans Lin-14 Temporal Gradient Formation. Genes & Development, 10, 3041-3050.
http://dx.doi.org/10.1101/gad.10.23.3041

[7]   Moss, E.G., Lee, R.C. and Ambros, V. (1997) The Cold Shock Domain Protein LIN-28 Controls Developmental Timing in C. elegans and Is Regulated by the Lin-4 RNA. Cell, 88, 637-646.
http://dx.doi.org/10.1016/S0092-8674(00)81906-6

[8]   Olsen, P.H. and Ambros, V. (1999) The Lin-4 Regulatory RNA Controls Developmental Timing in Caenorhabditis elegans by Blocking LIN-14 Protein Synthesis after the Initiation of Translation. Developmental Biology, 216, 671-680.
http://dx.doi.org/10.1006/dbio.1999.9523

[9]   Reinhart, B.J., Slack, F.J., Basson, M., Pasquinelli, A.E., Bettinger, J.C., et al. (2000) The 21-Nucleotide Let-7 RNA Regulates Developmental Timing in Caenorhabditis elegans. Nature, 403, 901-906.
http://dx.doi.org/10.1038/35002607

[10]   Waterston, R. and Sulston, J. (1998) The Human Genome Project: Reaching the Finish Line. Science, 282, 53-54.
http://dx.doi.org/10.1126/science.282.5386.53

[11]   Adams, M.D., Celniker, S.E., Holt, R.A., Evans, C.A., Gocayne, J.D., et al. (2000) The Genome Sequence of Drosophila Melanogaster. Science, 287, 2185-2195. http://dx.doi.org/10.1126/science.287.5461.2185

[12]   Venter, J.C., Adams, M.D., Myers, E.W., Li, P.W., Mural, R.J., et al. (2001) The Sequence of the Human Genome. Science, 291, 1304-1351. http://dx.doi.org/10.1126/science.1058040

[13]   Chinwalla, A.T., Cook, L.L., Delehaunty, K.D., Fewell, G.A., Fulton, L.A., et al. (2002) Initial Sequencing and Comparative Analysis of the Mouse Genome. Nature, 420, 520-562. http://dx.doi.org/10.1038/nature01262

[14]   Pasquinelli, A.E., Reinhart, B.J., Slack, F., Martindale, M.Q., Kuroda, M.I., et al. (2000) Conservation of the Sequence and Temporal Expression of Let-7 Heterochronic Regulatory RNA. Nature, 408, 86-89.
http://dx.doi.org/10.1038/35040556

[15]   Lau, N.C., Lim, L.P., Weinstein, E.G. and Bartel, D.P. (2001) An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans. Science, 294, 858-862. http://dx.doi.org/10.1126/science.1065062

[16]   Lagos-Quintana, M., Rauhut, R., Yalcin, A., Meyer, J., Lendeckel, W., et al. (2002) Identification of Tissue-Specific microRNAs from Mouse. Current Biology, 12, 735-739. http://dx.doi.org/10.1016/S0960-9822(02)00809-6

[17]   Aravin, A.A., Lagos-Quintana, M., Yalcin, A., Zavolan, M., Marks, D., et al. (2003) The Small RNA Profile during Drosophila melanogaster Development. Developmental Cell, 5, 337-350.
http://dx.doi.org/10.1016/S1534-5807(03)00228-4

[18]   Grad, Y., Aach, J., Hayes, G.D., Reinhart, B.J., Church, G.M., et al. (2003) Computational and Experimental Identification of C. elegans microRNAs. Molecular Cell, 11, 1253-1263. http://dx.doi.org/10.1016/S1097-2765(03)00153-9

[19]   Lagos-Quintana, M., Rauhut, R., Meyer, J., Borkhardt, A. and Tuschl, T. (2003) New microRNAs from Mouse and Human. RNA, 9, 175-179. http://dx.doi.org/10.1261/rna.2146903

[20]   Lim, L.P., Lau, N.C., Weinstein, E.G., Abdelhakim, A., Yekta, S., et al. (2003) The microRNAs of Caenorhabditis elegans. Genes & Development, 17, 991-1008. http://dx.doi.org/10.1101/gad.1074403

[21]   Ambros, V. (2004) The Functions of Animal microRNAs. Nature, 431, 350-355.
http://dx.doi.org/10.1038/nature02871

[22]   Bartel, D.P. (2004) MicroRNAs: Genomics, Biogenesis, Mechanism, and Function. Cell, 116, 281-297.
http://dx.doi.org/10.1016/S0092-8674(04)00045-5

[23]   Bentwich, I., Avniel, A., Karov, Y., Aharonov, R., Gilad, S., et al. (2005) Identification of Hundreds of Conserved and Nonconserved Human microRNAs. Nature Genetics, 37, 766-770. http://dx.doi.org/10.1038/ng1590

[24]   Chen, P.Y., Manninga, H., Slanchev, K., Chien, M., Russo, J.J., et al. (2005) The Developmental miRNA Profiles of Zebrafish as Determined by Small RNA Cloning. Genes & Development, 19, 1288-1293.
http://dx.doi.org/10.1101/gad.1310605

[25]   Watanabe, T., Takeda, A., Mise, K., Okuno, T., Suzuki, T., et al. (2005) Stage-Specific Expression of microRNAs during Xenopus Development. FEBS Letters, 579, 318-324. http://dx.doi.org/10.1016/j.febslet.2004.11.067

[26]   Ruby, J.G., Stark, A., Johnston, W.K., Kellis, M., Bartel, D.P., et al. (2007) Evolution, Biogenesis, Expression, and Target Predictions of a Substantially Expanded Set of Drosophila microRNAs. Genome Research, 17, 1850-1864.
http://dx.doi.org/10.1101/gr.6597907

[27]   Thatcher, E.J., Paydar, I., Anderson, K.K. and Patton, J.G. (2008) Regulation of Zebrafish Fin Regeneration by microRNAs. PNAS, 105, 18384-18389. http://dx.doi.org/10.1073/pnas.0803713105

[28]   Glazov, E.A., Cottee, P.A., Barris, W.C., Moore, R.J., Dalrymple, B.P., et al. (2008) A microRNA Catalog of the Developing Chicken Embryo Identified by a Deep Sequencing Approach. Genome Research, 18, 957-964.
http://dx.doi.org/10.1101/gr.074740.107

[29]   He, P.-A., Nie, Z., Chen, J., Chen, J., Lv, Z., et al. (2008) Identification and Characteristics of microRNAs from Bombyx mori. BMC Genomics, 9, 248. http://dx.doi.org/10.1186/1471-2164-9-248

[30]   Yu, X., Zhou, Q., Li, S.C., Luo, Q., Cai, Y., et al. (2008) The Silkworm (Bombyx mori) microRNAs and Their Expressions in Multiple Developmental Stages. PLoS One, 3, e2997. http://dx.doi.org/10.1371/journal.pone.0002997

[31]   Chen, X., Li, Q., Wang, J., Guo, X., Jiang, X., et al. (2009) Identification and Characterization of Novel Amphioxus microRNAs by Solexa Sequencing. Genome Biology, 10, R78. http://dx.doi.org/10.1186/gb-2009-10-7-r78

[32]   Shi, W., Hendrix, D., Levine, M. and Haley, B. (2009) A Distinct Class of Small RNAs Arises from Pre-miRNA-Proximal Regions in a Simple Chordate. Nature Structural & Molecular Biology, 16, 183-189.
http://dx.doi.org/10.1038/nsmb.1536

[33]   Wheeler, B.M., Heimberg, A.M., Moy, V.N., Sperling, E.A., Holstein, T.W., et al. (2009) The Deep Evolution of Metazoan microRNAs. Evolution & Development, 11, 50-68. http://dx.doi.org/10.1111/j.1525-142X.2008.00302.x

[34]   Hendrix, D., Levine, M. and Shi, W. (2010) Method miRTRAP, a Computational Method for the Systematic Identification of miRNAs from High Throughput Sequencing Data. Genome Biology, 11, R39.
http://dx.doi.org/10.1186/gb-2010-11-4-r39

[35]   Keshavan, R., Virata, M., Keshavan, A. and Zeller, R.W. (2010) Computational Identification of Ciona intestinalis microRNAs. Zoological Science, 27, 162-170. http://dx.doi.org/10.2108/zsj.27.162

[36]   Berezikov, E., Robine, N., Samsonova, A., Westholm, J.O., Naqvi, A., Hung, J.H., Okamura, K., Dai, Q., Bortolamiol-Becet, D., Martin, R., Zhao, Y.J., Zamore, P.D., Hannon, G.J., Marra, M.A., Weng, Z.P., Perrimon, N. and Lai, E.C. (2011) Deep Annotation of Drosophila Melanogaster microRNAs Yields Insights into Their Processing, Modification, and Emergence. Genome Research, 21, 203-215. http://dx.doi.org/10.1101/gr.116657.110

[37]   Lai, E.C. (2003) microRNAs: Runts of the Genome Assert Themselves. Current Biology, 13, R925-R936.
http://dx.doi.org/10.1016/j.cub.2003.11.017

[38]   Du, T. and Zamore, P.D. (2005) microPrimer: The Biogenesis and Function of microRNA. Development, 132, 4645-4652. http://dx.doi.org/10.1242/dev.02070

[39]   Kim, V.N., Han, J. and Siomi, M.C. (2009) Biogenesis of Small RNAs in Animals. Nature Reviews Molecular Cell Biology, 10, 126-139. http://dx.doi.org/10.1038/nrm2632

[40]   Lai, E.C. (2004) Predicting and Validating microRNA Targets. Genome Biology, 5, 115.
http://dx.doi.org/10.1186/gb-2004-5-9-115

[41]   Aboobaker, A.A., Tomancak, P., Patel, N., Rubin, G.M. and Lai, E.C. (2005) Drosophila microRNAs Exhibit Diverse Spatial Expression Patterns during Embryonic Development. Proceedings of the National Academy of Sciences of the United States of America, 102, 18017-18022.
http://dx.doi.org/10.1073/pnas.0508823102

[42]   Chen, J. and Zeller, R. (2009) Regulation of Gene Expression by the microRNA miR-124 in the Developing Nervous System of C. Intestinalis. ACSESS Proceedings AP0904, San Diego, 27 March 2009, 1-6.

[43]   Chen, J.S., San Pedro, M. and Zeller, R.W. (2011) miR-124 Function during Ciona intestinalis Neuronal Development Includes Extensive Interaction with the Notch Signaling Pathway. Development, 138, 4943-4953.
http://dx.doi.org/10.1242/dev.068049

[44]   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.

[45]   Zisoulis, D.G., Lovci, M.T., Wilbert, M.L., Hutt, K.R., Liang, T.Y., Pasquinelli, A.E. and Yeo, G.W. (2010) Comprehensive Discovery of Endogenous Argonaute Binding Sites in Caenorhabditis elegans. Nature Structural & Molecular Biology, 17, 173-179. http://dx.doi.org/10.1038/nsmb.1745

[46]   Krichevsky, A.M., King, K.S., Donahue, C.P., Khrapko, K. and Kosik, K.S. (2003) A microRNA Array Reveals Extensive Regulation of microRNAs during Brain Development. RNA, 9, 1274-1281.
http://dx.doi.org/10.1261/rna.5980303

[47]   Ruby, J.G., Jan, C., Player, C., Axtell, M.J., Lee, W., Nusbaum, C., Ge, H. and Bartel, D.P. (2006) Large-Scale Sequencing Reveals 21U-RNAs and Additional microRNAs and Endogenous siRNAs in C. elegans. Cell, 127, 1193-1207. http://dx.doi.org/10.1016/j.cell.2006.10.040

[48]   Kozomara, A. and Griffiths-Jones, S. (2011) miRbase: Integrating microRNA Annotation and Deep-Sequencing Data. Nucleic Acids Research, 39, D152-D157. http://dx.doi.org/10.1093/nar/gkq1027

[49]   Landgraf, P., Rusu, M., Sheridan, R., Sewer, A., Iovino, N., et al. (2007) A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing. Cell, 129, 1401-1414. http://dx.doi.org/10.1016/j.cell.2007.04.040

[50]   Hertel, J., Lindemeyer, M., Missal, K., Fried, C., Tanzer, A., Flamm, C., Hofacker, I.L., Stadler, P.F. and The Students of Bioinformatics Computer Labs 2004 and 2005 (2006) The Expansion of the Metazoan microRNA Repertoire. BMC Genomics, 7, 25. http://dx.doi.org/10.1186/1471-2164-7-25

[51]   Okamura, K., Phillips, M.D., Tyler, D.M., Duan, H., Chou, Y.T. and La, E.C. (2008) The Regulatory Activity of microRNA* Species Has Substantial Influence on microRNA and 3’UTR Evolution. Nature Structural & Molecular Biology, 15, 354-363. http://dx.doi.org/10.1038/nsmb.1409

[52]   Yang, J.S., Phillips, M.D., Betel, D., Mu, P., Ventura, A., Siepel, A.C., Chen, K.C. and Lai, E.C. (2011) Widespread Regulatory Activity of Vertebrate microRNA* Species. RNA, 17, 312-326. http://dx.doi.org/10.1261/rna.2537911

[53]   Fire, A., Xu, S., Montgomery, M.K., Kostas, S.A., Driver, S.E. and Mello, C.C. (1998) Potent and Specific Genetic Interference by Double-Stranded RNA in Caenorhabditis elegans. Nature, 391, 806-811.
http://dx.doi.org/10.1038/35888

[54]   Kim, D.H. and Rossi, J.J. (2007) Strategies for Silencing Human Disease Using RNA Interference. Nature Reviews Genetics, 8, 173-184. http://dx.doi.org/10.1038/nrg2006

[55]   Elbashir, S.M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K. and Tuschl, T. (2001) Duplexes of 21-Nucleotide RNAs Mediate RNA Interference in Cultured Mammalian Cells. Nature, 411, 494-498.
http://dx.doi.org/10.1038/35078107

[56]   McFarland, T.J., Zhang, Y., Appukuttan, B. and Stout, J.T. (2004) Gene Therapy for Proliferative Ocular Diseases. Expert Opinion on Biological Therapy, 4, 1053-1058. http://dx.doi.org/10.1517/14712598.4.7.1053

[57]   Bitko, V., Musiyenko, A., Shulyayeva, O. and Barik, S. (2004) Inhibition of Respiratory Viruses by Nasally Administered siRNA. Nature Medicine, 11, 50-55. http://dx.doi.org/10.1038/nm1164

[58]   Rossi, J.J. (2006) RNAi as a Treatment for HIV-1 Infection. Biotechniques, 40, S25-S29.
http://dx.doi.org/10.2144/000112167

[59]   Dykxhoorn, D.M. and Lieberman, J. (2006) Silencing Viral Infection. PLoS Medicine, 3, e242.
http://dx.doi.org/10.1371/journal.pmed.0030242

[60]   Raoul, C., Barker, S. and Aebischer, P. (2005) Viral-Based Modelling and Correction of Neurodegenerative Diseases by RNA Interference. Gene Therapy, 13, 487-495. http://dx.doi.org/10.1038/sj.gt.3302690

[61]   Pai, S., Lin, Y., Macaes, B., Meneshian, A., Hung, C. and Wu, T.C. (2005) Prospects of RNA Interference Therapy for Cancer. Gene Therapy, 13, 464-477. http://dx.doi.org/10.1038/sj.gt.3302694

[62]   Stegmeier, F., Hu, G., Rickles, R.J., Hannon, G.J. and Elledge, S.J. (2005) A Lentiviral microRNA-Based System for Single-Copy Polymerase II-Regulated RNA Interference in Mammalian Cells. Proceedings of the National Academy of Sciences of the United States of America, 102, 13212-13217. http://dx.doi.org/10.1073/pnas.0506306102

[63]   Dykxhoorn, D.M., Novina, C.D. and Sharp, P.A. (2003) Killing the Messenger: Short RNAs that Silence Gene Expression. Nature Reviews Molecular Cell Biology, 4, 457-467. http://dx.doi.org/10.1038/nrm1129

[64]   Dickins, R.A., Hemann, M.T., Zilfou, J.T., Simpson, D.R., Ibarra, I., Hannon, G.J. and Lowe, S.W. (2005) Probing Tumor Phenotypes Using Stable and Regulated Synthetic microRNA Precursors. Nature Genetics, 37, 1289-1295.

[65]   Silva, J.M., Li, M.Z., Chang, K., Ge, W., Golding, M.C., et al. (2005) Second-Generation shRNA Libraries Covering the Mouse and Human Genomes. Nature Genetics, 37, 1281-1288.

[66]   Sarnova, L., Malik, R., Sedlacek, R. and Svoboda, P. (2010) Shortcomings of Short Hairpin RNA-Based Transgenic RNA Interference in Mouse Oocytes. Journal of Negative Results in Biomedicine, 9, 8.

[67]   Chung, K.H., Hart, C.C., Al-Bassam, S., Avery, A., Taylor, J., Patel, P.D., Vojtek, A.B. and Turner, D.L. (2006) Polycistronic RNA Polymerase II Expression Vectors for RNA Interference Based on Bic/miR-155. Nucleic Acids Research, 34, e53. http://dx.doi.org/10.1093/nar/gkl143

[68]   Zeng, Y., Wagner, E.J. and Cullen, B.R. (2002) Both Natural and Designed Micro RNAs Can Inhibit the Expression of Cognate mRNAs when Expressed in Human Cells. Molecular Cell, 9, 1327-1333.
http://dx.doi.org/10.1016/S1097-2765(02)00541-5

[69]   Du, G., Yonekubo, J., Zeng, Y., Osisami, M. and Frohman, M.A. (2006) Design of Expression Vectors for RNA Interference Based on miRNAs and RNA Splicing. FEBS Journal, 273, 5421-5427.
http://dx.doi.org/10.1111/j.1742-4658.2006.05534.x

[70]   De Veer, M.J., Sledz, C.A. and Williams, B.R. (2005) Detection of Foreign RNA: Implications for RNAi. Immunology and Cell Biology, 83, 224-228. http://dx.doi.org/10.1111/j.1440-1711.2005.01337.x

[71]   Ossowski, S., Schwab, R. and Weigel, D. (2008) Gene Silencing in Plants Using Artificial microRNAs and Other Small RNAs. The Plant Journal, 53, 674-690. http://dx.doi.org/10.1111/j.1365-313X.2007.03328.x

[72]   Niu, Q.W., Lin, S.S., Reyes, J.L., Chen, K.C., Wu, H.W., Yeh, S.D. and Chua, N.H. (2006) Expression of Artificial microRNAs in Transgenic Arabidopsis Thaliana Confers Virus Resistance. Nature Biotechnology, 24, 1420-1428.
http://dx.doi.org/10.1038/nbt1255

[73]   Schwab, R., Ossowski, S., Riester, M., Warthmann, N. and Weigel, D. (2006) Highly Specific Gene Silencing by Artificial microRNAs in Arabidopsis. The Plant Cell Online, 18, 1121-1133. http://dx.doi.org/10.1105/tpc.105.039834

[74]   Zhang, X., Li, H., Zhang, J., Zhang, C., Gong, P., Ziaf, K., Xiao, F.M. and Ye, Z.B. (2011) Expression of Artificial microRNAs in Tomato Confers Efficient and Stable Virus Resistance in a Cell-Autonomous Manner. Transgenic Research, 20, 569-581. http://dx.doi.org/10.1007/s11248-010-9440-3

[75]   Molnar, A., Bassett, A., Thuenemann, E., Schwach, F., Karkare, S., Ossowski, S., Weigel, D. and Baulcombe, D. (2009) Highly Specific Gene Silencing by Artificial microRNAs in the Unicellular Alga Chlamydomonas reinhardtii. The Plant Journal, 58, 165-174. http://dx.doi.org/10.1111/j.1365-313X.2008.03767.x

[76]   Zhao, T., Wang, W., Bai, X. and Qi, Y. (2009) Gene Silencing by Artificial microRNAs in Chlamydomonas. The Plant Journal, 58, 157-164. http://dx.doi.org/10.1111/j.1365-313X.2008.03758.x

[77]   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. Molecular Cell, 27, 91-105.
http://dx.doi.org/10.1016/j.molcel.2007.06.017

[78]   Joyce Tang, W., Chen, J.S. and Zeller, R.W. (2013) Transcriptional Regulation of the Peripheral Nervous System in Ciona intestinalis. Developmental Biology, 378, 183-193. http://dx.doi.org/10.1016/j.ydbio.2013.03.016

[79]   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. http://dx.doi.org/10.1016/j.cell.2004.12.035

[80]   Clark, A.M., Goldstein, L.D., Tevlin, M., Tavare, S., Shaham, S. and Miska, E.A. (2010) The microRNA miR-124 Controls Gene Expression in the Sensory Nervous System of Caenorhabditis elegans. Nucleic Acids Research, 38, 3780-3793. http://dx.doi.org/10.1093/nar/gkq083

[81]   Kertesz, M., Iovino, N., Unnerstall, U., Gaul, U. and Segal, E. (2007) The Role of Site Accessibility in microRNA Target Recognition. Nature Genetics, 39, 1278-1284. http://dx.doi.org/10.1038/ng2135

[82]   Brennecke, J., Stark, A., Russell, R.B. and Cohen, S.M. (2005) Principles of microRNA-Target Recognition. PLoS Biology, 3, Article ID: e85. http://dx.doi.org/10.1371/journal.pbio.0030085

[83]   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. Molecular Cell, 38, 789-802.
http://dx.doi.org/10.1016/j.molcel.2010.06.005

[84]   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. http://dx.doi.org/10.1016/j.cell.2013.03.043

[85]   Hafner, M., Landthaler, M., Burger, L., Khorshid, M., Hausser, J., et al. (2010) Transcriptomewide Identification of RNA-Binding Protein and microRNA Target Sites by PAR-CLIP. Cell, 141, 129-141.
http://dx.doi.org/10.1016/j.cell.2010.03.009

[86]   Zeng, Y. and Cullen, B.R. (2005) Efficient Processing of Primary microRNA Hairpins by Drosha Requires Flanking Nonstructured RNA Sequences. Journal of Biological Chemistry, 280, 27595-27603.
http://dx.doi.org/10.1074/jbc.M504714200

[87]   Tang, R., Li, L., Zhu, D., Hou, D., Cao, T., Gu, H.W., Zhang, J., Chen, J.Y., Zhang, C.Y. and Zen, K. (2011) Mouse miRNA-709 Directly Regulates miRNA-15a/16-1 Biogenesis at the Posttranscriptional Level in the Nucleus: Evidence for a microRNA Hierarchy System. Cell Research, 22, 504-515. http://dx.doi.org/10.1038/cr.2011.137

[88]   Zisoulis, D.G., Kai, Z.S., Chang, R.K. and Pasquinelli, A.E. (2012) Autoregulation of microRNA Biogenesis by let-7 and Argonaute. Nature, 486, 541-544. http://dx.doi.org/10.1038/nature11134

[89]   Wilbert, M.L., Huelga, S.C., Kapeli, K., Stark, T.J., Liang, T.Y., et al. (2012) LIN28 Binds Messenger RNAs at GGAGA Motifs and Regulates Splicing Factor Abundance. Molecular Cell, 48, 195-206.
http://dx.doi.org/10.1016/j.molcel.2012.08.004

[90]   Van Wynsberghe, P.M., Kai, Z.S., Massirer, K.B., Burton, V.H., Yeo, G.W. and Pasquinelli, A.E. (2011) LIN-28 Co-Transcriptionally Binds Primary let-7 to Regulate miRNA Maturation in Caenorhabditis elegans. Nature Structural & Molecular Biology, 18, 302-308. http://dx.doi.org/10.1038/nsmb.1986

[91]   Neilsen, C.T., Goodall, G.J. and Bracken, C.P. (2012) IsomiRs-the Overlooked Repertoire in the Dynamic microRNAome. Trends in Genetics, 28, 544-549. http://dx.doi.org/10.1016/j.tig.2012.07.005

[92]   Zhou, H., Arcila, M.L., Li, Z., Lee, E.J., Henzler, C., Liu, J.Y., Rana, T.M. and Kosik, K.S. (2012) Deep Annotation of Mouse iso-miR and iso-moR Variation. Nucleic Acids Research, 40, 5864-5875. http://dx.doi.org/10.1093/nar/gks247

 
 
Top