[PDF][PDF] A transcriptome-wide translational program defined by LIN28B expression level

FE Tan, S Sathe, EC Wheeler, JK Nussbacher, S Peter… - Molecular cell, 2019 - cell.com
FE Tan, S Sathe, EC Wheeler, JK Nussbacher, S Peter, GW Yeo
Molecular cell, 2019cell.com
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 …
Summary
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.
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