Flexible pri-miRNA structures enable tunable production of 5’ isomiRs

References

• Gebert LFR, MacRae IJ. Regulation of microRNA function in animals. Nat Rev Mol Cell Biol. 2019;20:21–37.
   PubMed Web of Science ®Google Scholar
• Lin S, Gregory RI. MicroRNA biogenesis pathways in cancer. Nat Rev Cancer. 2015;15:321–333.
   PubMed Web of Science ®Google Scholar
• Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014;15:509–524.
   PubMed Web of Science ®Google Scholar
• Khvorova A, Reynolds A, Jayasena SD. Functional siRNAs and miRNAs exhibit strand bias. Cell. 2003;115:209–216.
   PubMed Web of Science ®Google Scholar
• Schwarz DS, Hutvágner G, Du T, et al. Asymmetry in the assembly of the RNAi enzyme complex. Cell. 2003;115:199–208.
   PubMed Web of Science ®Google Scholar
• Jonas S, Izaurralde E. Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet. 2015;16:421–433.
   PubMed Web of Science ®Google Scholar
• Iwakawa H-O, Tomari Y. The functions of MicroRNAs: mRNA decay and translational repression. Trends Cell Biol. 2015;25:651–665.
   PubMed Web of Science ®Google Scholar
• Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–233.
   PubMed Web of Science ®Google Scholar
• Fromm B, Billipp T, Peck LE, et al. A uniform system for the annotation of vertebrate microRNA genes and the evolution of the human microRNAome. Annu Rev Genet. 2015;49:213–242.
   PubMed Web of Science ®Google Scholar
• Nguyen TA, Jo MH, Choi Y-G, et al. Functional anatomy of the human microprocessor. Cell. 2015;161:1374–1387.
   PubMed Web of Science ®Google Scholar
• Han J, Lee Y, Yeom K-H, et al. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell. 2006;125:887–901.
   PubMed Web of Science ®Google Scholar
• Zeng Y, Yi R, Cullen BR. Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J. 2005;24(1):138–148.
   PubMed Web of Science ®Google Scholar
• Rice GM, Shivashankar V, Ma EJ, et al. Functional atlas of primary miRNA maturation by the microprocessor. Molecular Cell. 2020;80(5):892–902.e4.
   PubMed Web of Science ®Google Scholar
• Treiber T, Treiber N, Plessmann U, et al. A compendium of RNA-binding proteins that regulate MicroRNA biogenesis. Molecular Cell. 2017;66(2):270–284.e13.
   PubMed Web of Science ®Google Scholar
• Fang W, Bartel DP. The menu of features that define primary MicroRNAs and enable De Novo design of MicroRNA genes. Molecular Cell. 2015;60(1):131–145.
   PubMed Web of Science ®Google Scholar
• Auyeung VC, Ulitsky I, McGeary SE, et al. Beyond secondary structure: primary-sequence determinants license pri-miRNA hairpins for processing. Cell. 2013;152(4):844–858.
   PubMed Web of Science ®Google Scholar
• Kwon SC, Baek SC, Choi Y-G, et al. Molecular basis for the single-nucleotide precision of primary microRNA processing. Molecular Cell. 2019;73(3):505–518.e5.
   PubMed Web of Science ®Google Scholar
• Ma H, Wu Y, Choi J-G, et al. Lower and upper stem-single-stranded RNA junctions together determine the Drosha cleavage site. Proc Natl Acad Sci USA. 2013;110(51):20687–20692.
   PubMed Web of Science ®Google Scholar
• Roden C, Gaillard J, Kanoria S, et al. Novel determinants of mammalian primary microRNA processing revealed by systematic evaluation of hairpin-containing transcripts and human genetic variation. Genome Res. 2017;27(3):374–384.
   PubMed Web of Science ®Google Scholar
• Burke JM, Kelenis DP, Kincaid RP, et al. A central role for the primary microRNA stem in guiding the position and efficiency of Drosha processing of a viral pri-miRNA. RNA. 2014;20(7):1068–1077.
   PubMed Web of Science ®Google Scholar
• Li S, Nguyen TD, Nguyen TL, et al. Mismatched and wobble base pairs govern primary microRNA processing by human Microprocessor. Nature Communications. 2020;11(1):1926.
   PubMed Web of Science ®Google Scholar
• Bofill-De Ros X, Kasprzak WK, Bhandari Y, et al. Structural differences between Pri-miRNA paralogs promote alternative Drosha cleavage and expand target repertoires. Cell Rep. 2019;26(2):447–459.e4.
   PubMed Web of Science ®Google Scholar
• McCall MN, Kim M-S, Adil M, et al. Toward the human cellular microRNAome. Genome Res. 2017;27(10):1769–1781.
   PubMed Web of Science ®Google Scholar
• Berezikov E, Robine N, Samsonova A, et al. Deep annotation of Drosophila melanogaster microRNAs yields insights into their processing, modification, and emergence. Genome Res. 2011;21(2):203–215.
   PubMed Web of Science ®Google Scholar
• Shi W, Hendrix D, Levine M, et al. A distinct class of small RNAs arises from pre-miRNA–proximal regions in a simple chordate. Nature Structural & Molecular Biology. 2009;16(2):183–189.
   PubMed Web of Science ®Google Scholar
• Varani G, McClain WH. The G·U wobble base pair. EMBO Reports. 2000;1(1):18–23.
   PubMed Web of Science ®Google Scholar
• Zhang H, Kolb FA, Jaskiewicz L, et al. Single processing center models for human Dicer and bacterial RNase III. Cell. 2004;118(1):57–68.
   PubMed Web of Science ®Google Scholar
• Macrae IJ, Zhou K, Li F, et al. Structural basis for double-stranded RNA processing by Dicer. Science. 2006;311(5758):195–198.
   PubMed Web of Science ®Google Scholar
• Zhu L, Kandasamy SK, Fukunaga R. Dicer partner protein tunes the length of miRNAs using base-mismatch in the pre-miRNA stem. Nucleic Acids Res. 2018;46(7):3726–3741.
   PubMed Web of Science ®Google Scholar
• Park J-E, Heo I, Tian Y, et al. Dicer recognizes the 5′ end of RNA for efficient and accurate processing. Nature. 2011;475(7355):201–205.
   PubMed Web of Science ®Google Scholar
• He M, Liu Y, Wang X, et al. Cell-type-based analysis of microRNA profiles in the mouse brain. Neuron. 2012;73(1):35–48.
   PubMed Web of Science ®Google Scholar
• Kim K, Nguyen TD, Li S, et al. SRSF3 recruits DROSHA to the basal junction of primary microRNAs. RNA. 2018;24(7):892–898.
   PubMed Web of Science ®Google Scholar
• Nussbacher JK, Yeo GW. Systematic Discovery of RNA Binding Proteins that Regulate MicroRNA Levels. Molecular Cell. 2018;69(6):1005–1016.e7.
   PubMed Web of Science ®Google Scholar
• Partin AC, Zhang K, Jeong B-C, et al. Cryo-EM structures of human Drosha and DGCR8 in complex with primary MicroRNA. Molecular Cell. 2020;78(3):411–422.e4.
   PubMed Web of Science ®Google Scholar
• Jin W, Wang J, Liu C-P, et al. Structural Basis for pri-miRNA Recognition by Drosha. Molecular Cell. 2020;78(3):423–433.e5.
   PubMed Web of Science ®Google Scholar
• Sun L, Fazal FM, Li P, et al. RNA structure maps across mammalian cellular compartments. Nature Structural & Molecular Biology. 2019;26(4):322–330.
   PubMed Web of Science ®Google Scholar
• Luo Q-J, Zhang J, Li P, et al. RNA structure probing reveals the structural basis of Dicer binding and cleavage. Nature Communications. 2021;12(1):3397.
   PubMed Web of Science ®Google Scholar
• Kim K, Baek SC, Lee -Y-Y, et al. A quantitative map of human primary microRNA processing sites. Molecular Cell. 2021;81(16):3422–3439.e11.
   PubMed Web of Science ®Google Scholar
• Kim B, Jeong K, Kim VN. Genome-wide mapping of DROSHA cleavage sites on primary MicroRNAs and noncanonical substrates. Molecular Cell. 2017;66(2):258–269.e5.
   PubMed Web of Science ®Google Scholar
• Kang W, Fromm B, Houben AJS, et al. MapToCleave: High-throughput profiling of microRNA biogenesis in living cells. Cell Rep. 2021. Nov 16;37(7):110015. doi:10.1016/j.celrep.2021.110015. PMID: 34788611.
   Web of Science ®Google Scholar
• Dai L, Chen K, Youngren B, et al. Cytoplasmic Drosha activity generated by alternative splicing. Nucleic Acids Res. 2016;44(21):10454–10466.
   PubMed Web of Science ®Google Scholar
• Sim S-E, Lim C-S, Kim J-I, et al. The brain-enriched MicroRNA miR-9-3p regulates synaptic plasticity and memory. The Journal of Neuroscience. 2016;36(33):8641–8652.
   PubMed Web of Science ®Google Scholar
• Bofill-De Ros X, Chen K, Chen S, et al. QuagmiR: a cloud-based application for isomiR big data analytics. Bioinformatics. 2019;35(9):1576–1578.
   PubMed Web of Science ®Google Scholar
• Bofill-De Ros X, Luke B, Guthridge R, et al. Tumor IsomiR Encyclopedia (TIE): a pan-cancer database of miRNA isoforms. Bioinformatics. 2021;37(18):3023–3025.
   PubMed Web of Science ®Google Scholar
• Gruber AR, Lorenz R, Bernhart SH, et al. The Vienna RNA websuite. Nucleic Acids Res. 2008;36(Web Server):W70–4.
   PubMed Web of Science ®Google Scholar
• Kozomara A, Birgaoanu M, Griffiths-Jones S. miRBase: from microRNA sequences to function. Nucleic Acids Res. 2019;47(D1):D155–D162.
   PubMed Web of Science ®Google Scholar
• Fromm B, Domanska D, Høye E, et al. MirGeneDB 2.0: the metazoan microRNA complement. Nucleic Acids Res. 2020;48(D1):D132–D141.
   PubMed Web of Science ®Google Scholar