hnRNP C is a key regulator of protein synthesis in mitosis

Stringent post-transcriptional regulation of mRNA fate is critical for proper cell division. To detect proteins involved in such regulation, we analyzed the composition of intact polysomal complexes from mitotic and interphase cells by quantitative mass-spectrometry. Using this approach, we detected increased association of several mRNA-binding proteins, including heterogeneous nuclear ribonucleoprotein C (hnRNP C), with mitotic polysomes. Immunofluorescence analysis, puromycin-sensitivity assays and nascent-chain pulldowns confirmed that hnRNP C interacts with polysome-bound mRNA during mitosis. Using a combination of pulsed SILAC and metabolic labeling, we found that knockdown of hnRNP C has a pervasive effect on both global and transcript-specific translation rates. Furthermore, ribosome profiling revealed that hnRNP C is involved in translation of mRNAs encoding components of the translation machinery and other mRNAs harboring a 5' terminal oligopyrimidine tract (5’ TOP). Taken together, these results suggest that hnRNP C is crucial for ribogenesis during mitosis; in its absence, production of ribosomal proteins and translation factors is impaired and translation rates are reduced during subsequent phases of the cell cycle.