A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes

ABSTRACT: The rate of RNA Polymerase II (RNAPII) elongation has an important role in the control of Alternative splicing (AS); however, the in vivo consequences of an altered elongation rate are unknown. Here, we generated mouse embryonic stem cells (ESCs) knocked-in for a slow elongating form of RNAPII. We show that a reduced transcriptional elongation rate results in early embryonic lethality in mice. Focusing on neuronal differentiation as a model, we observed that slow elongation impairs development of the neural lineage from ESCs, which is accompanied by changes in AS and in gene expression along this pathway. In particular, we found a crucial role for RNAPII elongation rate in transcription and splicing of long neuronal genes involved in synapse signaling. The impact of the kinetic coupling of

SUBMITTER: Magdalena, M Maslon 

PROVIDER: S-SCDT-EMBOJ-2018-101244 | biostudies-other |

REPOSITORIES: biostudies-other