Conserved regulation of RNA processing in somatic cell reprogramming

Along with the reorganization of epigenetic and transcriptional networks, somatic cell reprogramming brings about numerous changes at the level of RNA processing. These include the expression of specific transcript isoforms and 3' untranslated regions. A number of studies have uncovered RNA processing factors that modulate the efficiency of the reprogramming process. However, a comprehensive evaluation of the involvement of RNA processing factors in the reprogramming of somatic mammalian cells is lacking.

Here, we used data from a large number of studies carried out in three mammalian species, mouse, chimpanzee and human, to uncover consistent changes in gene expression upon reprogramming of somatic cells. We found that a core set of nine splicing factors have consistent changes across the majority of data sets in all three species. Most striking among these are ESRP1 and ESRP2, which accelerate and enhance the efficiency of somatic cell reprogramming by promoting isoform expression changes associated with mesenchymal-to-epithelial transition. We further identify genes and processes in which splicing changes are observed in both human and mouse.

Our results provide a general resource for gene expression and splicing changes that take place during somatic cell reprogramming. Furthermore, they support the concept that splicing factors with evolutionarily conserved, cell type-specific expression can modulate the efficiency of the process by reinforcing intermediate states resembling the cell types in which these factors are normally expressed.