Lin28 is highly expressed in human and mouse embryonic stem (ES) cells. Here, we show that in mouse ES cells, specific repression of Lin28 results in decreased cell proliferation, while overexpression of Lin28 accelerates cell proliferation. Further, Lin28 associates specifically with ribonucleoprotein particles containing mRNAs for cyclins A and B and cdk4. Importantly, changes in Lin28 levels lead to corresponding changes in the levels of these proteins, and sequences from the 3' untranslated regions of cyclin B and cdk4 mRNAs exhibit stimulatory effects on translation of reporter genes in a Lin28-dependent fashion. Thus, we postulate that Lin28 may play a role in the regulation of translation of genes important for the growth and maintenance of pluripotent cells.

Lin28 has been shown to block the processing of let-7 microRNAs implicated in the regulation of cell growth and differentiation. Here, we show that Lin28 also specifically associates with ribonucleoprotein particles containing the replication-dependent histone H2a mRNA in mouse embryonic stem cells. We further show that the coding region of H2a mRNA harbors high affinity binding sequences for Lin28 and that these sequences stimulate the expression of reporter genes in a Lin28-dependent manner. We suggest that a key function of Lin28 in the maintenance of pluripotency is to promote the expression of the H2a gene (and perhaps also other replication-dependent histone genes) at the posttranscriptional level in order to coordinate histone production with the unique proliferative properties of embryonic stem cells.