XPO5 promotes primary miRNA processing independently of RanGTP Journal Article
| Authors: | Wang, J.; Lee, J. E.; Riemondy, K.; Yu, Y.; Marquez, S. M.; Lai, E. C.; Yi, R. |
| Article Title: | XPO5 promotes primary miRNA processing independently of RanGTP |
| Abstract: | XPO5 mediates nuclear export of miRNA precursors in a RanGTP-dependent manner. However, XPO5-associated RNA species have not been determined globally and it is unclear whether XPO5 has any additional functions other than nuclear export. Here we show XPO5 pervasively binds to double-stranded RNA regions found in some clustered primary miRNA precursors and many cellular RNAs. Surprisingly, the binding of XPO5 to pri-miRNAs such as mir-17~92 and mir-15b~16-2 and highly structured RNAs such as vault RNAs is RanGTP-independent. Importantly, XPO5 enhances the processing efficiency of pri-mir-19a and mir-15b~16-2 by the DROSHA/DGCR8 microprocessor. Genetic deletion of XPO5 compromises the biogenesis of most miRNAs and leads to severe defects during mouse embryonic development and skin morphogenesis. This study reveals an unexpected function of XPO5 for recognizing and facilitating the nuclear cleavage of clustered pri-miRNAs, identifies numerous cellular RNAs bound by XPO5, and demonstrates physiological functions of XPO5 in mouse development. © 2020, The Author(s). |
| Keywords: | immunohistochemistry; controlled study; protein expression; unclassified drug; gene mutation; human cell; gene deletion; nonhuman; comparative study; animal cell; mouse; microrna; gene expression; signaling; genetic association; developmental biology; embryo development; morphogenesis; physiology; skin; rna binding protein; rna; genetic transfection; cell culture; messenger rna; protein purification; gestational age; immunoprecipitation; plasmid; real time polymerase chain reaction; molecular biology; rna structure; transfer rna; structure analysis; rna processing; bioinformatics; biochemistry; gel mobility shift assay; guanine nucleotide binding protein; embryonic development; complementary dna; rna extraction; dicer; double stranded rna; argonaute 2 protein; rna sequence; northern blotting; physiological response; dissociation constant; rna analysis; rna isolation; dna hairpin; exportin 5; rna purification; nuclear rna; immune dysregulation; high throughput sequencing; microrna 17; microrna 16; microrna 19a; human; article; argonaute 3 protein; microrna 15b; microrna 30a; rna fragment |
| Journal Title: | Nature Communications |
| Volume: | 11 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2020-04-15 |
| Start Page: | 1845 |
| Language: | English |
| DOI: | 10.1038/s41467-020-15598-x |
| PUBMED: | 32296071 |
| PROVIDER: | scopus |
| PMCID: | PMC7160132 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2020 -- Source: Scopus |
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