The stem cell–specific protein TRIM71 inhibits maturation and activity of the prodifferentiation miRNA let-7 via two independent molecular mechanisms

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FIGURE 8.
FIGURE 8.

TRIM71 directly binds and stabilizes let-7 targets in ESCs. (A) Schematic representation for the analysis conducted in BD. Genes commonly down-regulated in all Trim71 mutant ESCs (yellow)—obtained from B—are enriched for let-7 targets (blue) (Supplemental Table 2). Genes found enriched (greater than twofold) in TRIM71 RNA-IPs in ESCs (green) were overlapped with genes commonly down-regulated in all Trim71 mutant ESCs (yellow)—overlap depicted in C—to identify genes bound and stabilized by TRIM71 in ESCs. For those genes, miRNA enrichment analysis was conducted (Supplemental Table 3) to identify let-7 targets bound and stabilized by TRIM71 (orange). (B) Coexpression network analysis for the indicated ESC lines using an available data set (GSE134125) revealed genes commonly down-regulated in all Trim71 mutant ESCs (modules B, C, J, and K, marked with a yellow asterisk). (C) Overlap of TRIM71 RNA-IP data in ESCs (GSE134125) with gene expression data, showing the number of TRIM71-bound mRNAs in ESCs within each module from B. (D) miRNA network showing targets for the different let-7 family members found among commonly down-regulated genes in all Trim71 mutant ESCs (modules B, C, J, and K from B), with let-7 targets directly bound by TRIM71 in ESCs marked in orange. See also Supplemental Tables 2, 3.

This Article

  1. RNA 27: 805-828