Dual strategies for Argonaute2-mediated biogenesis of erythroid miRNAs underlie conserved requirements for slicing in mammals Journal Article


Authors: Jee, D.; Yang, J. S.; Park, S. M.; Farmer, D. T.; Wen, J.; Chou, T.; Chow, A.; McManus, M. T.; Kharas, M. G.; Lai, E. C.
Article Title: Dual strategies for Argonaute2-mediated biogenesis of erythroid miRNAs underlie conserved requirements for slicing in mammals
Abstract: While Slicer activity of Argonaute is central to RNAi, conserved roles of slicing in endogenous regulatory biology are less clear, especially in mammals. Biogenesis of erythroid Dicer-independent mir-451 involves Ago2 catalysis, but mir-451-KO mice do not phenocopy Ago2 catalytic-dead (Ago2-CD) mice, suggesting other needs for slicing. Here, we reveal mir-486 as another dominant erythroid miRNA with atypical biogenesis. While it is Dicer dependent, it requires slicing to eliminate its star strand. Thus, in Ago2-CD conditions, miR-486-5p is functionally inactive due to duplex arrest. Genome-wide analyses reveal miR-486 and miR-451 as the major slicing-dependent miRNAs in the hematopoietic system. Moreover, mir-486-KO mice exhibit erythroid defects, and double knockout of mir-486/451 phenocopies the cell-autonomous effects of Ago2-CD in the hematopoietic system. Finally, we observe that Ago2 is the dominant-expressed Argonaute in maturing erythroblasts, reflecting a specialized environment for processing slicing-dependent miRNAs. Overall, the mammalian hematopoietic system has evolved multiple conserved requirements for Slicer-dependent miRNA biogenesis. Jee et al. reveal that a major conserved rationale for mammalian Argonaute2 slicing is for the combined maturation of miR-486 and miR-451, miRNAs necessary for erythroid development. Their loss phenocopies the erythroid defects of slicing-deficient mice, and this slicing requirement explains the unique Ago2-only expression pattern found in erythroid tissue. © 2018 Elsevier Inc.
Keywords: controlled study; protein expression; unclassified drug; nonhuman; genetic analysis; animal cell; mouse; animal tissue; microrna; cell maturation; erythroblast; erythroid precursor cell; erythropoiesis; animal experiment; gene locus; genome-wide association study; enzyme activity; mammal; hematopoietic system; catalysis; knockout mouse; biogenesis; dicer; ribonuclease iii; argonaute 2 protein; rnai; argonaute; microrna 183; mirna; mir-451; slicer; microrna 451; ago2; hematopoietic; article; microrna 486; mir-486; microrna 342; microrna 486 3p
Journal Title: Molecular Cell
Volume: 69
Issue: 2
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2018-01-18
Start Page: 265
End Page: 278.e6
Language: English
DOI: 10.1016/j.molcel.2017.12.027
PROVIDER: scopus
PMCID: PMC5824974
PUBMED: 29351846
DOI/URL:
Notes: Article -- Export Date: 1 March 2018 -- Source: Scopus
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MSK Authors
  1. Eric C Lai
    119 Lai
  2. Jr-Shiuan Yang
    13 Yang
  3. Jiayu Wen
    11 Wen
  4. Michael Kharas
    54 Kharas
  5. Sun Mi Park
    15 Park
  6. David   Jee
    4 Jee
  7. Arthur W Chow
    13 Chow
  8. Timothy Chou
    11 Chou