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Dynamics of MicroRNA Biogenesis

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Biophysics of RNA-Protein Interactions

Part of the book series: Biological and Medical Physics, Biomedical Engineering ((BIOMEDICAL))

Abstract

MicroRNAs (miRNAs) are a class of short non-coding RNAs (~22 nt) that play important gene-regulatory functions in nearly all biological processes in eukaryotic organisms. Mature miRNAs are loaded into an Argonaute (Ago) protein effector and guide the nucleoprotein complex to recognize and silence target RNAs post-transcriptionally. This chapter outlines our current understanding of miRNA biogenesis from its initial transcription to the processing by the microprocessor in the nucleus, to the nuclear export and the cytoplasmic maturation by the endoribonuclease Dicer. This book chapter focuses on recent biophysical and single-molecule studies that have revealed important molecular bases and dynamic processes governing the biogenesis of microRNA with an unprecedented high spatiotemporal resolution, thus, uncovering hidden steps and intermediate conformations that are difficult to obtain using conventional approaches.

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References

  1. Ha, M., & Kim, V. N. (2014). Regulation of microRNA biogenesis. Nature Reviews Molecular Cell Biology, 15, 509–524.

    Article  Google Scholar 

  2. Huntzinger, E., & Izaurralde, E. (2011). Gene silencing by microRNAs: Contributions of translational repression and mRNA decay. Nature Reviews Genetics, 12, 99–110.

    Article  Google Scholar 

  3. Krol, J., Loedige, I., & Filipowicz, W. (2010). The widespread regulation of microRNA biogenesis, function and decay. Nature Reviews Genetics, 11, 597–610.

    Article  Google Scholar 

  4. Calin, G. A., & Croce, C. M. (2006). MicroRNA signatures in human cancers. Nature Reviews Cancer, 6, 857–866.

    Article  Google Scholar 

  5. Nicoloso, M. S., Spizzo, R., Shimizu, M., Rossi, S., & Calin, G. A. (2009). MicroRNAs–the micro steering wheel of tumour metastases. Nature Reviews Cancer, 9, 293–302.

    Article  Google Scholar 

  6. Fareh, M., Turchi, L., Virolle, V., Debruyne, D., Almairac, F., de-la-Forest Divonne, et al. (2012). The miR 302-367 cluster drastically affects self-renewal and infiltration properties of glioma-initiating cells through CXCR4 repression and consequent disruption of the SHH-GLI-NANOG network. Cell Death and Differentiation, 19, 232–244.

    Article  Google Scholar 

  7. Fareh, M., Almairac, F., Turchi, L., Burel-Vandenbos, F., Paquis, P., Fontaine, D., et al. (2017). Cell-based therapy using miR-302-367 expressing cells represses glioblastoma growth. Cell Death and Disease, 8, e2713.

    Article  Google Scholar 

  8. Lee, R. C., Feinbaum, R. L., & Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 75, 843–854.

    Article  Google Scholar 

  9. Wightman, B., Ha, I., & 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.

    Article  Google Scholar 

  10. Bartel, D. P. (2018). Metazoan MicroRNAs. Cell, 173, 20–51.

    Article  Google Scholar 

  11. Berezikov, E. (2011). Evolution of microRNA diversity and regulation in animals. Nature Reviews Genetics, 12, 846–860.

    Article  Google Scholar 

  12. Kim, V. N., & Nam, J. W. (2006). Genomics of microRNA. Trends in genetics: TIG, 22, 165–173.

    Article  ADS  Google Scholar 

  13. Lee, Y., Jeon, K., Lee, J. T., Kim, S., & Kim, V. N. (2002). MicroRNA maturation: Stepwise processing and subcellular localization. The EMBO Journal, 21, 4663–4670.

    Article  Google Scholar 

  14. Cai, X., Hagedorn, C. H., & Cullen, B. R. (2004). Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA, 10, 1957–1966.

    Article  Google Scholar 

  15. Lee, Y., Kim, M., Han, J., Yeom, K. H., Lee, S., Baek, S. H., et al. (2004). MicroRNA genes are transcribed by RNA polymerase II. The EMBO Journal, 23, 4051–4060.

    Article  Google Scholar 

  16. Li, K., Li, Z., Zhao, N., Xu, Y., Liu, Y., Zhou, Y., et al. (2013). Functional analysis of microRNA and transcription factor synergistic regulatory network based on identifying regulatory motifs in non-small cell lung cancer. BMC Systems Biology, 7, 122.

    Article  Google Scholar 

  17. O’Donnell, K. A., Wentzel, E. A., Zeller, K. I., Dang, C. V., & Mendell, J. T. (2005). c-Myc-regulated microRNAs modulate E2F1 expression. Nature, 435, 839–843.

    Article  ADS  Google Scholar 

  18. Ma, L., Young, J., Prabhala, H., Pan, E., Mestdagh, P., Muth, D., et al. (2010). miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nature Cell Biology, 12, 247–256.

    Article  Google Scholar 

  19. Chang, T. C., Yu, D., Lee, Y. S., Wentzel, E. A., Arking, D. E., West, K. M., et al. (2008). Widespread microRNA repression by Myc contributes to tumorigenesis. Nature Genetics, 40, 43–50.

    Article  Google Scholar 

  20. Mestdagh, P., Fredlund, E., Pattyn, F., Schulte, J. H., Muth, D., Vermeulen, J., et al. (2010). MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors. Oncogene, 29, 1394–1404.

    Article  Google Scholar 

  21. Barros-Silva, D., Costa-Pinheiro, P., Duarte, H., Sousa, E. J., Evangelista, A. F., Graca, I., et al. (2018). MicroRNA-27a-5p regulation by promoter methylation and MYC signaling in prostate carcinogenesis. Cell Death and Disease, 9, 167.

    Article  Google Scholar 

  22. Song, S. J., Poliseno, L., Song, M. S., Ala, U., Webster, K., Ng, C., et al. (2013). MicroRNA-antagonism regulates breast cancer stemness and metastasis via TET-family-dependent chromatin remodeling. Cell, 154, 311–324.

    Article  Google Scholar 

  23. Gregory, R. I., Yan, K. P., Amuthan, G., Chendrimada, T., Doratotaj, B., Cooch, N., et al. (2004). The Microprocessor complex mediates the genesis of microRNAs. Nature, 432, 235–240.

    Article  ADS  Google Scholar 

  24. Lee, Y., Ahn, C., Han, J., Choi, H., Kim, J., Yim, J., et al. (2003). The nuclear RNase III Drosha initiates microRNA processing. Nature, 425, 415–419.

    Article  ADS  Google Scholar 

  25. Han, J., Lee, Y., Yeom, K. H., Kim, Y. K., Jin, H., & Kim, V. N. (2004). The Drosha-DGCR25 complex in primary microRNA processing. Genes & Development, 18, 3016–3027.

    Article  Google Scholar 

  26. Kwon, S. C., Nguyen, T. A., Choi, Y. G., Jo, M. H., Hohng, S., Kim, V. N., et al. (2016). Structure of human DROSHA. Cell, 164, 81–90.

    Article  Google Scholar 

  27. Nguyen, T. A., Jo, M. H., Choi, Y. G., Park, J., Kwon, S. C., Hohng, S., et al. (2015). Functional anatomy of the human microprocessor. Cell, 161, 1374–1387.

    Article  Google Scholar 

  28. Han, J., Lee, Y., Yeom, K. H., Nam, J. W., Heo, I., Rhee, J. K., et al. (2006). Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR28 complex. Cell, 125, 887–901.

    Article  Google Scholar 

  29. Fang, W., & Bartel, D. P. (2015). The menu of features that define primary MicroRNAs and enable De Novo design of MicroRNA genes. Molecular Cell, 60, 131–145.

    Article  Google Scholar 

  30. Auyeung, V. C., Ulitsky, I., McGeary, S. E., & Bartel, D. P. (2013). Beyond secondary structure: Primary-sequence determinants license pri-miRNA hairpins for processing. Cell, 152, 844–858.

    Article  Google Scholar 

  31. Denli, A. M., Tops, B. B., Plasterk, R. H., Ketting, R. F., & Hannon, G. J. (2004). Processing of primary microRNAs by the microprocessor complex. Nature, 432, 231–235.

    Article  ADS  Google Scholar 

  32. Sellier, C., Hwang, V. J., Dandekar, R., Durbin-Johnson, B., Charlet-Berguerand, N., Ander, B. P., etal. (2014). Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome. PloS one, 9, e103884.

    Article  ADS  Google Scholar 

  33. Bartel, D. P. (2004). MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell, 116, 281–297.

    Article  Google Scholar 

  34. Stark, K. L., Xu, B., Bagchi, A., Lai, W. S., Liu, H., Hsu, R., et al. (2008). Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. Nature Genetics, 40, 751–760.

    Article  Google Scholar 

  35. Fenelon, K., Mukai, J., Xu, B., Hsu, P. K., Drew, L. J., Karayiorgou, M., et al. (2011). Deficiency of Dgcr8, a gene disrupted by the 22q11.2 microdeletion, results in altered short-term plasticity in the prefrontal cortex. Proceedings of the National Academy of Sciences of the United States of America, 108, 4447–4452.

    Article  ADS  Google Scholar 

  36. Fareh, M., Loeff, L., Szczepaniak, M., Haagsma, A. C., Yeom, K. H., & Joo, C. (2016). Single-molecule pull-down for investigating protein-nucleic acid interactions. Methods, 105, 99–108.

    Article  Google Scholar 

  37. Doye, V., & Hurt, E. (1997). From nucleoporins to nuclear pore complexes. Current Opinion in Cell Biology, 9, 401–411.

    Article  Google Scholar 

  38. Beck, M., & Hurt, E. (2017). The nuclear pore complex: Understanding its function through structural insight. Nature reviews. Molecular cell biology, 18, 73–89.

    Article  Google Scholar 

  39. Raices, M., & D’Angelo, M. A. (2012). Nuclear pore complex composition: A new regulator of tissue-specific and developmental functions. Nature Reviews Molecular Cell Biology, 13, 687–699.

    Article  Google Scholar 

  40. Grossman, E., Medalia, O., & Zwerger, M. (2012). Functional architecture of the nuclear pore complex. Annual Review of Biophysics, 41, 557–584.

    Article  Google Scholar 

  41. Finlay, D. R., Meier, E., Bradley, P., Horecka, J., & Forbes, D. J. (1991). A complex of nuclear pore proteins required for pore function. The Journal of Cell Biology, 114, 169–183.

    Article  Google Scholar 

  42. Hinshaw, J. E., Carragher, B. O., & Milligan, R. A. (1992). Architecture and design of the nuclear pore complex. Cell, 69, 1133–1141.

    Article  Google Scholar 

  43. Akey, C. W., & Radermacher, M. (1993). Architecture of the Xenopus nuclear pore complex revealed by three-dimensional cryo-electron microscopy. The Journal of Cell Biology, 122, 1–19.

    Article  Google Scholar 

  44. Kosinski, J., Mosalaganti, S., von Appen, A., Teimer, R., DiGuilio, A. L., Wan, W., et al. (2016). Molecular architecture of the inner ring scaffold of the human nuclear pore complex. Science, 352, 363–365.

    Article  ADS  Google Scholar 

  45. Eibauer, M., Pellanda, M., Turgay, Y., Dubrovsky, A., Wild, A., & Medalia, O. (2015). Structure and gating of the nuclear pore complex. Nature communications, 6, 7532.

    Article  ADS  Google Scholar 

  46. Okamura, M., Inose, H., & Masuda, S. (2015). RNA export through the NPC in eukaryotes. Genes, 6, 124–149.

    Article  Google Scholar 

  47. Kohler, A., & Hurt, E. (2007). Exporting RNA from the nucleus to the cytoplasm. Nature Reviews Molecular Cell Biology, 8, 761–773.

    Article  Google Scholar 

  48. Mattaj, I. W., & Englmeier, L. (1998). Nucleocytoplasmic transport: The soluble phase. Annual Review of Biochemistry, 67, 265–306.

    Article  Google Scholar 

  49. Gorlich, D., & Kutay, U. (1999). Transport between the cell nucleus and the cytoplasm. Annual Review of Cell and Developmental Biology, 15, 607–660.

    Article  Google Scholar 

  50. Izaurralde, E., & Adam, S. (1998). Transport of macromolecules between the nucleus and the cytoplasm. RNA, 4, 351–364.

    Google Scholar 

  51. Pemberton, L. F., Blobel, G., & Rosenblum, J. S. (1998). Transport routes through the nuclear pore complex. Current Opinion in cell Biology, 10, 392–399.

    Article  Google Scholar 

  52. Hurt, E. C. (1988). A novel nucleoskeletal-like protein located at the nuclear periphery is required for the life cycle of Saccharomyces cerevisiae. The EMBO Journal, 7, 4323–4334.

    Article  Google Scholar 

  53. Doye, V., & Hurt, E. C. (1995). Genetic approaches to nuclear pore structure and function. Trends in Genetics: TIG, 11, 235–241.

    Article  Google Scholar 

  54. Lowe, A. R., Siegel, J. J., Kalab, P., Siu, M., Weis, K., & Liphardt, J. T. (2010). Selectivity mechanism of the nuclear pore complex characterized by single cargo tracking. Nature, 467, 600–603.

    Article  ADS  Google Scholar 

  55. Grunwald, D., Singer, R. H., & Rout, M. (2011). Nuclear export dynamics of RNA-protein complexes. Nature, 475, 333–341.

    Article  Google Scholar 

  56. Moore, M. S., & Blobel, G. (1993). The GTP-binding protein Ran/TC4 is required for protein import into the nucleus. Nature, 365, 661–663.

    Article  ADS  Google Scholar 

  57. Moroianu, J. (1999). Nuclear import and export pathways. Journal of Cellular Biochemistry, (Suppl 32–33), 76–83.

    Article  Google Scholar 

  58. Rodriguez, M. S., Dargemont, C., & Stutz, F. (2004). Nuclear export of RNA. Biology of the Cell, 96, 639–655.

    Article  Google Scholar 

  59. Lund, E., Guttinger, S., Calado, A., Dahlberg, J. E., & Kutay, U. (2004). Nuclear export of microRNA precursors. Science, 303, 95–98.

    Article  ADS  Google Scholar 

  60. Yi, R., Qin, Y., Macara, I. G., & Cullen, B. R. (2003). Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes & Development, 17, 3011–3016.

    Article  Google Scholar 

  61. Zeng, Y., & Cullen, B. R. (2004). Structural requirements for pre-microRNA binding and nuclear export by Exportin 5. Nucleic Acids Research, 32, 4776–4785.

    Article  Google Scholar 

  62. Bohnsack, M. T., Czaplinski, K., & Gorlich, D. (2004). Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA, 10, 185–191.

    Article  Google Scholar 

  63. 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 Reports, 6, 211–221.

    Article  Google Scholar 

  64. Khudayberdiev, S. A., Zampa, F., Rajman, M., & Schratt, G. (2013). A comprehensive characterization of the nuclear microRNA repertoire of post-mitotic neurons. Frontiers in Molecular Neuroscience, 6, 43.

    Article  Google Scholar 

  65. Liao, J. Y., Ma, L. M., Guo, Y. H., Zhang, Y. C., Zhou, H., Shao, P., et al. (2010). Deep sequencing of human nuclear and cytoplasmic small RNAs reveals an unexpectedly complex subcellular distribution of miRNAs and tRNA 3′ trailers. PloS One, 5, e10563.

    Article  ADS  Google Scholar 

  66. Pitchiaya, S., Heinicke, L. A., Park, J. I., Cameron, E. L., & Walter, N. G. (2017). Resolving subcellular miRNA trafficking and turnover at single-molecule resolution. Cell Reports, 19, 630–642.

    Article  Google Scholar 

  67. Grunwald, D., & Singer, R. H. (2010). In vivo imaging of labelled endogenous beta-actin mRNA during nucleocytoplasmic transport. Nature, 467, 604–607.

    Article  ADS  Google Scholar 

  68. Stockley, P. G., Stonehouse, N. J., Murray, J. B., Goodman, S. T., Talbot, S. J., Adams, C. J., et al. (1995). Probing sequence-specific RNA recognition by the bacteriophage MS2 coat protein. Nucleic Acids Research, 23, 2512–2518.

    Article  Google Scholar 

  69. Yang, W., & Musser, S. M. (2006). Nuclear import time and transport efficiency depend on importin beta concentration. The Journal of Cell Biology, 174, 951–961.

    Article  Google Scholar 

  70. Yang, W., Gelles, J., & Musser, S. M. (2004). Imaging of single-molecule translocation through nuclear pore complexes. Proceedings of the National Academy of Sciences of the United States of America, 101, 12887–12892.

    Article  ADS  Google Scholar 

  71. Sun, C., Yang, W., Tu, L. C., & Musser, S. M. (2008). Single-molecule measurements of importin alpha/cargo complex dissociation at the nuclear pore. Proceedings of the National Academy of Sciences of the United States of America, 105, 8613–8618.

    Article  ADS  Google Scholar 

  72. Noland, C. L., & Doudna, J. A. (2013). Multiple sensors ensure guide strand selection in human RNAi pathways. RNA, 19, 639–648.

    Article  Google Scholar 

  73. Tants, J. N., Fesser, S., Kern, T., Stehle, R., Geerlof, A., Wunderlich, C., et al. (2017). Molecular basis for asymmetry sensing of siRNAs by the Drosophila Loqs-PD/Dcr-2 complex in RNA interference. Nucleic Acids Research, 45, 12536–12550.

    Article  Google Scholar 

  74. Meijer, H. A., Smith, E. M., & Bushell, M. (2014). Regulation of miRNA strand selection: Follow the leader? Biochemical Society Transactions, 42, 1135–1140.

    Article  Google Scholar 

  75. Noland, C. L., Ma, E., & Doudna, J. A. (2011). siRNA repositioning for guide strand selection by human Dicer complexes. Molecular Cell, 43, 110–121.

    Article  Google Scholar 

  76. Filipowicz, W., Bhattacharyya, S. N., & Sonenberg, N. (2008). Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight? Nature Reviews Genetics, 9, 102–114.

    Article  Google Scholar 

  77. Guo, L., & Lu, Z. (2010). The fate of miRNA* strand through evolutionary analysis: Implication for degradation as merely carrier strand or potential regulatory molecule? PloS One, 5, e11387.

    Article  ADS  Google Scholar 

  78. Chandradoss, S. D., Schirle, N. T., Szczepaniak, M., MacRae, I. J., & Joo, C. (2015). A dynamic search process underlies MicroRNA targeting. Cell, 162, 96–107.

    Article  Google Scholar 

  79. Klein, M., Chandradoss, S. D., Depken, M., & Joo, C. (2017). Why Argonaute is needed to make microRNA target search fast and reliable. Seminars in Cell & Developmental Biology, 65, 20–28.

    Article  Google Scholar 

  80. Grishok, A., Pasquinelli, A. E., Conte, D., Li, N., Parrish, S., Ha, I., et al. (2001). Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell, 106, 23–34.

    Article  Google Scholar 

  81. Kim, Y. K., Kim, B., & Kim, V. N. (2016). Re-evaluation of the roles of DROSHA, Export in 5, and DICER in microRNA biogenesis. Proceedings of the National Academy of Sciences of the United States of America, 113, E1881–E1889.

    Article  ADS  Google Scholar 

  82. Bernstein, E., Kim, S. Y., Carmell, M. A., Murchison, E. P., Alcorn, H., Li, M. Z., et al. (2003). Dicer is essential for mouse development. Nature Genetics, 35, 215–217.

    Article  Google Scholar 

  83. Krill, K. T., Gurdziel, K., Heaton, J. H., Simon, D. P., & Hammer, G. D. (2013). Dicer deficiency reveals microRNAs predicted to control gene expression in the developing adrenal cortex. Molecular Endocrinology, 27, 754–768.

    Article  Google Scholar 

  84. Mori, M. A., Thomou, T., Boucher, J., Lee, K. Y., Lallukka, S., Kim, J. K., et al. (2014). Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy. The Journal of Clinical Investigation, 124, 3339–3351.

    Article  Google Scholar 

  85. Mudhasani, R., Zhu, Z., Hutvagner, G., Eischen, C. M., Lyle, S., Hall, L. L., et al. (2008). Loss of miRNA biogenesis induces p19Arf-p53 signaling and senescence in primary cells. The Journal of Cell Biology, 181, 1055–1063.

    Article  Google Scholar 

  86. Soukup, G. A., Fritzsch, B., Pierce, M. L., Weston, M. D., Jahan, I., McManus, M. T., et al. (2009). Residual microRNA expression dictates the extent of inner ear development in conditional Dicer knockout mice. Developmental Biology, 328, 328–341.

    Article  Google Scholar 

  87. Chen, J. F., Murchison, E. P., Tang, R., Callis, T. E., Tatsuguchi, M., Deng, Z., et al. (2008). Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure. Proceedings of the National Academy of Sciences of the United States of America, 105, 2111–2116.

    Article  ADS  Google Scholar 

  88. Macrae, I. J., Zhou, K., Li, F., Repic, A., Brooks, A. N., Cande, W. Z., et al. (2006). Structural basis for double-stranded RNA processing by Dicer. Science, 311, 195–198.

    Article  ADS  Google Scholar 

  89. MacRae, I. J., Zhou, K., & Doudna, J. A. (2007). Structural determinants of RNA recognition and cleavage by Dicer. Nature Structural & Molecular Biology, 14, 934–940.

    Article  Google Scholar 

  90. Lau, P. W., Potter, C. S., Carragher, B., & MacRae, I. J. (2009). Structure of the human Dicer-TRBP complex by electron microscopy. Structure, 17, 1326–1332.

    Article  Google Scholar 

  91. Zhang, H., Kolb, F. A., Jaskiewicz, L., Westhof, E., & Filipowicz, W. (2004). Single processing center models for human Dicer and bacterial RNase III. Cell, 118, 57–68.

    Article  Google Scholar 

  92. Lau, P. W., Guiley, K. Z., De, N., Potter, C. S., Carragher, B., & MacRae, I. J. (2012). The molecular architecture of human Dicer. Nature Structural & Molecular Biology, 19, 436–440.

    Article  Google Scholar 

  93. Park, J. E., Heo, I., Tian, Y., Simanshu, D. K., Chang, H., Jee, D., et al. (2011). Dicer recognizes the 5′ end of RNA for efficient and accurate processing. Nature, 475, 201–205.

    Article  Google Scholar 

  94. Tian, Y., Simanshu, D. K., Ma, J. B., Park, J. E., Heo, I., Kim, V. N., et al. (2014). A phosphate-binding pocket within the platform-PAZ-connector helix cassette of human Dicer. Molecular Cell, 53, 606–616.

    Article  Google Scholar 

  95. Tsutsumi, A., Kawamata, T., Izumi, N., Seitz, H., & Tomari, Y. (2011). Recognition of the pre-miRNA structure by Drosophila Dicer-1. Nature Structural & Molecular Biology, 18, 1153–1158.

    Article  Google Scholar 

  96. Gu, S., Jin, L., Zhang, Y., Huang, Y., Zhang, F., Valdmanis, P. N., et al. (2012). The loop position of shRNAs and pre-miRNAs is critical for the accuracy of dicer processing in vivo. Cell, 151, 900–911.

    Article  Google Scholar 

  97. Liu, Z., Wang, J., Cheng, H., Ke, X., Sun, L., Zhang, Q. C., et al. (2018). Cryo-EM structure of human Dicer and its complexes with a Pre-miRNA substrate. Cell, 173, 1549–1550.

    Article  Google Scholar 

  98. Lee, H. Y., Zhou, K., Smith, A. M., Noland, C. L., & Doudna, J. A. (2013). Differential roles of human Dicer-binding proteins TRBP and PACT in small RNA processing. Nucleic Acids Research, 41, 6568–6576.

    Article  Google Scholar 

  99. Chakravarthy, S., Sternberg, S. H., Kellenberger, C. A., & Doudna, J. A. (2010). Substrate-specific kinetics of Dicer-catalyzed RNA processing. Journal of Molecular Biology, 404, 392–402.

    Article  Google Scholar 

  100. Wilson, R. C., Tambe, A., Kidwell, M. A., Noland, C. L., Schneider, C. P., & Doudna, J. A. (2015). Dicer-TRBP complex formation ensures accurate mammalian microRNA biogenesis. Molecular Cell, 57, 397–407.

    Article  Google Scholar 

  101. Kim, Y., Yeo, J., Lee, J. H., Cho, J., Seo, D., Kim, J. S., et al. (2014). Deletion of human tarbp2 reveals cellular microRNA targets and cell-cycle function of TRBP. Cell Reports, 9, 1061–1074.

    Article  Google Scholar 

  102. Ota, H., Sakurai, M., Gupta, R., Valente, L., Wulff, B. E., Ariyoshi, K., et al. (2013). ADAR1 forms a complex with Dicer to promote microRNA processing and RNA-induced gene silencing. Cell, 153, 575–589.

    Article  Google Scholar 

  103. Yamashita, S., Nagata, T., Kawazoe, M., Takemoto, C., Kigawa, T., Guntert, P., et al. (2011). Structures of the first and second double-stranded RNA-binding domains of human TAR RNA-binding protein. Protein Science: A Publication of the Protein Society, 20, 118–130.

    Article  Google Scholar 

  104. Schmedt, C., Green, S. R., Manche, L., Taylor, D. R., Ma, Y., & Mathews, M. B. (1995). Functional characterization of the RNA-binding domain and motif of the double-stranded RNA-dependent protein kinase DAI (PKR). Journal of Molecular Biology, 249, 29–44.

    Article  Google Scholar 

  105. Krovat, B. C., & Jantsch, M. F. (1996). Comparative mutational analysis of the double-stranded RNA binding domains of Xenopus laevis RNA-binding protein A. The Journal of Biological Chemistry, 271, 28112–28119.

    Article  Google Scholar 

  106. Takahashi, T., Miyakawa, T., Zenno, S., Nishi, K., Tanokura, M., & Ui-Tei, K. (2013). Distinguishable in vitro binding mode of monomeric TRBP and dimeric PACT with siRNA. PloS One, 8, e63434.

    Article  ADS  Google Scholar 

  107. Daniels, S. M., & Gatignol, A. (2012). The multiple functions of TRBP, at the hub of cell responses to viruses, stress, and cancer. Microbiology and Molecular Biology Reviews: MMBR, 76, 652–666. https://mmbr.asm.org/content/76/3/652.abstract; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429622/

    Article  Google Scholar 

  108. Masliah, G., Maris, C., Konig, S. L., Yulikov, M., Aeschimann, F., Malinowska, A. L., et al. (2018). Structural basis of siRNA recognition by TRBP double-stranded RNA binding domains. The EMBO Journal, 37, e97089. https://doi.org/10.15252/embj.201797089.

  109. Ryter, J. M., & Schultz, S. C. (1998). Molecular basis of double-stranded RNA-protein interactions: Structure of a dsRNA-binding domain complexed with dsRNA. The EMBO Journal, 17, 7505–7513.

    Article  Google Scholar 

  110. Masliah, G., Barraud, P., & Allain, F. H. (2013). RNA recognition by double-stranded RNA binding domains: A matter of shape and sequence. Cellular and Molecular Life Sciences: CMLS, 70, 1875–1895.

    Google Scholar 

  111. Koh, H. R., Kidwell, M. A., Ragunathan, K., Doudna, J. A., & Myong, S. (2013). ATP-independent diffusion of double-stranded RNA binding proteins. Proceedings of the National Academy of Sciences of the United States of America, 110, 151–156.

    Article  ADS  Google Scholar 

  112. Joo, C., McKinney, S. A., Nakamura, M., Rasnik, I., Myong, S., & Ha, T. (2006). Real-time observation of RecA filament dynamics with single monomer resolution. Cell, 126, 515–527.

    Article  Google Scholar 

  113. Joo, C., Balci, H., Ishitsuka, Y., Buranachai, C., & Ha, T. (2008). Advances in single-molecule fluorescence methods for molecular biology. Annual Review of Biochemistry, 77, 51–76.

    Article  Google Scholar 

  114. Abbondanzieri, E. A., Bokinsky, G., Rausch, J. W., Zhang, J. X., Le Grice, S. F., & Zhuang, X. (2008). Dynamic binding orientations direct activity of HIV reverse transcriptase. Nature, 453, 184–189.

    Article  ADS  Google Scholar 

  115. Lee, Y., Hur, I., Park, S. Y., Kim, Y. K., Suh, M. R., & Kim, V. N. (2006). The role of PACT in the RNA silencing pathway. The EMBO Journal, 25, 522–532.

    Article  Google Scholar 

  116. Benoit, M. P., Imbert, L., Palencia, A., Perard, J., Ebel, C., Boisbouvier, J., et al. (2013). The RNA-binding region of human TRBP interacts with microRNA precursors through two independent domains. Nucleic Acids Research, 41, 4241–4252.

    Article  Google Scholar 

  117. Hwang, H., & Myong, S. (2014). Protein induced fluorescence enhancement (PIFE) for probing protein-nucleic acid interactions. Chemical Society Reviews, 43, 1221–1229.

    Article  Google Scholar 

  118. Myong, S., Cui, S., Cornish, P. V., Kirchhofer, A., Gack, M. U., Jung, J. U., et al. (2009). Cytosolic viral sensor RIG-I is a 5′-triphosphate-dependent translocase on double-stranded RNA. Science, 323, 1070–1074.

    Article  ADS  Google Scholar 

  119. Wang, X., Vukovic, L., Koh, H. R., Schulten, K., & Myong, S. (2015). Dynamic profiling of double-stranded RNA binding proteins. Nucleic Acids Research, 43, 7566–7576.

    Article  Google Scholar 

  120. Koh, H. R., Kidwell, M. A., Doudna, J., & Myong, S. (2017). RNA scanning of a molecular machine with a built-in ruler. Journal of the American Chemical Society, 139, 262–268.

    Article  Google Scholar 

  121. Peltier, H. J., & Latham, G. J. (2008). Normalization of microRNA expression levels in quantitative RT-PCR assays: Identification of suitable reference RNA targets in normal and cancerous human solid tissues. RNA, 14, 844–852.

    Article  Google Scholar 

  122. Fareh, M., Yeom, K. H., Haagsma, A. C., Chauhan, S., Heo, I., & Joo, C. (2016). TRBP ensures efficient Dicer processing of precursor microRNA in RNA-crowded environments. Nature Communications, 7, 13694.

    Article  ADS  Google Scholar 

  123. Willig, K. I., Kellner, R. R., Medda, R., Hein, B., Jakobs, S., & Hell, S. W. (2006). Nanoscale resolution in GFP-based microscopy. Nature Methods, 3, 721–723.

    Article  Google Scholar 

  124. Rust, M. J., Bates, M., & Zhuang, X. (2006). Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nature Methods, 3, 793–795.

    Article  Google Scholar 

  125. Betzig, E., Patterson, G. H., Sougrat, R., Lindwasser, O. W., Olenych, S., Bonifacino, J. S., et al. (2006). Imaging intracellular fluorescent proteins at nanometer resolution. Science, 313, 1642–1645.

    Article  ADS  Google Scholar 

  126. Dean, K. M., & Palmer, A. E. (2014). Advances in fluorescence labeling strategies for dynamic cellular imaging. Nature Chemical Biology, 10, 512–523.

    Article  ADS  Google Scholar 

  127. Paige, J. S., Nguyen-Duc, T., Song, W., & Jaffrey, S. R. (2012). Fluorescence imaging of cellular metabolites with RNA. Science, 335, 1194.

    Article  ADS  Google Scholar 

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Acknowledgements

I thank Chirlmin Joo and Joe Trapani laboratory members for their help, support, and the insightful discussions. This work was supported by the Fondation pour la Recherche Medicale [SPE20120523964 to Mohamed Fareh]; and the Zero Childhood Cancer initiative in Australia led by Prof. Michelle Haber (executive director, Children’s Cancer Institute, Sydney, Australia) and Prof. Joe Trapani (head of Cancer Immunotherapy program, Peter MacCallum Cancer Centre, Melbourne, Australia).

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Fareh, M. (2019). Dynamics of MicroRNA Biogenesis. In: Joo, C., Rueda, D. (eds) Biophysics of RNA-Protein Interactions. Biological and Medical Physics, Biomedical Engineering. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-9726-8_10

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