A Transcriptome-wide Translational Program Defined by LIN28B Expression Level.

Abstract

LIN28 RNA binding proteins are dynamically expressed throughout mammalian development and during disease. However, it remains unclear how changes in LIN28 expression define patterns of post-transcriptional gene regulation. Here we show that LIN28 expression level is a key variable that sets the magnitude of protein translation. By systematically varying LIN28B protein levels in human cells, we discovered a dose-dependent divergence in transcriptome-wide ribosome occupancy that enabled the formation of two discrete translational subpopulations composed of nearly all expressed genes. This bifurcation in gene expression was mediated by a redistribution in Argonaute association, from let-7 to non-let-7 microRNA families, resulting in a global shift in cellular miRNA activity. Post-transcriptional effects were scaled across the physiological LIN28 expression range. Together, these data highlight the central importance of RBP expression level and its ability to encode regulation.