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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.

Histone H2a mRNA interacts with Lin28 and contains a Lin28-dependent posttranscriptional regulatory element