Embryonic stem cells (ESCs) undergo rapid proliferation with shorter cell cycle phases. This depends largely on the activity of the miR-290 and miR-302 microRNA (miRNA) families. A third miRNA, let-7, inhibits self-renewal and promotes differentiation of ESCs, but its activity is kept low in ESCs by the LIN28 protein. Gregory and colleagues have found that the let-7 target TRIM71 represses the expression of a negative modulator of G1–S transition: the cyclin-dependent kinase inhibitor, Cdkn1a (Nat. Commun. 3, 923; 2012). They observe high levels of TRIM71 in murine undifferentiated ESCs, but not in differentiated cell types. Using immunoprecipitation followed by mass spectrometry, they identify Argonaute 2 as a TRIM71 partner. They find that TRIM71 can be found in miRNA-associated catalytic RISC (RNA-induced silencing complex), which is responsible for miRNA-mediated repression and localizes to P-bodies (where this repression is thought to occur). Levels of the known miR-290/miR-302 target Cdkn1a were shown to increase following TRIM71 silencing. TRIM71 effects on Cdkn1 require an intact miRNA binding site, and occur post-transcriptionally. The authors observe that TRIM71 silencing decreases ESC proliferation, whereas overexpression promotes G1–S transition. Thus, the authors have delineated a functional crosstalk between let-7 and miR-290/miR-302. How TRIM71 affects miRNA-mediated effects on Cdkn1a remains to be investigated, as it does not seem to affect levels of miRNA or of the miRNA machinery.