Transcriptional elongation regulator 1 affects transcription and splicing of genes associated with cellular morphology and cytoskeleton dynamics and is required for neurite outgrowth in neuroblastoma cells and primary neuronal cultures.

Juan Pablo Muñoz-Cobo, Noemí Sánchez-Hernández, Sara Gutiérrez, Younes El Yousfi, Marta Montes, Carme Gallego, Cristina Hernández-Munain, and Carlos Suñé

Institute of Parasitology and Biomedicine "López Neyra" (IPBLN-CSIC) and Molecular Biology Institute of Barcelona (IBMB-CSIC)

Several neurodegenerative disorders are associated with alterations in dendrite morphology that lead to an impairment in neuronal connectivity and are the cause of neurological and cognitive disorders. One of the mechanisms that has been proposed to explain the effect of these alterations on diseases is the disturbance of the function of transcription and RNA processing factors, which may result in the deregulation of important neuronal genes. Here, we have studied the function of TCERG1, a transcription and splicing factor that has been implicated in Huntington's disease (HD) pathogenesis. We show that TCERG1 depletion led to widespread alterations in mRNA processing with considerable changes in the transcription and alternative splicing patterns of genes involved in cytoskeleton dynamics and neurite outgrowth. Accordingly, TCERG1 depletion in the neuroblastoma SH-SY5Y cell line and primary mouse neurons affected morphogenesis and resulted in reduced dendritic outgrowth, with a major effect on dendrite ramification and branching complexity. These defects could be rescued by ectopic expression of TCERG1. Our results indicate that TCERG1 affects expression of multiple mRNAs involved in neuron projection development, whose misregulation may be involved in TCERG1-linked neurological disorders.

TCERG1 affects dendritic outgrowth and branching in mouse hippocampal neurons. Immunofluorescence of individual neurons that were transiently transfected with either the non-targeting control shRNA (shControl) or the TCERG1-targeting shRNA together with a GFP vector. The morphology of the transfected cells was detected based on the GFP signal (green). Scale bar, 25 µm.

Transcriptional elongation regulator 1 affects transcription and splicing of genes associated with cellular morphology and cytoskeleton dynamics and is required for neurite outgrowth in neuroblastoma cells and primary neuronal cultures.

Molecular Neurobiology 2016 DOI 10.1007/s12035-016-0284-6