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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