KSRP silencing favors neural differentiation of P19 teratocarcinoma cells.

Understanding the molecular mechanisms that control the balance between multipotency and differentiation is of great importance to elucidate the genesis of both developmental disorders and cell transformation events. To investigate the role of the RNA binding protein KSRP in controlling neural differentiation, we used the P19 embryonal carcinoma cell line that is able to differentiate into neuron-like cells under appropriate culture conditions. We have recently reported that KSRP controls the differentiative fate of multipotent mesenchymal cells owing to its ability to promote decay of unstable transcripts and to favor maturation of selected micro-RNAs (miRNAs) from precursors.

Bone morphogenetic protein/SMAD signaling orients cell fate decision by impairing KSRP-dependent microRNA maturation.

MicroRNAs (miRNAs) are essential regulators of development, physiology, and evolution, and their biogenesis is strictly controlled at multiple levels. Regulatory proteins, such as KSRP, modulate rates and timing of enzymatic reactions responsible for maturation of select miRNAs from their primary transcripts in response to specific stimuli. Here, we show that KSRP silencing in mesenchymal C2C12 cells produces a change in the transcriptome largely overlapping that induced by bone morphogenetic protein 2 (BMP2) signaling activation.

KSRP, many functions for a single protein.

KSRP is a single-strand nucleic acids binding protein that affects RNA fate at multiple levels. KSRP modular structure and its complex pattern of post-translational modifications underpin the interaction with a wide spectrum of RNA target sequences, as well as with other RNA-binding proteins and molecular adaptors. These interactions are important to the regulation of different steps of mRNA metabolism and, in turn, modulate several aspects of cellular proliferation and differentiation.