Effect of TCERG1 on Cajal body assembly and snRNP biogenesis

Abstract

TCERG1 is a nuclear protein involved in transcription and splicing regulation. TCERG1 binds to transcription and splicing components, localizes at the interface of nuclear speckles and what are presumably nearby transcription/splicing sites, and affects the transcriptional activity of CCAAT / enhancer-binding protein alpha (CEBPA) and the alternative pre-mRNA splicing of several splicing reporters. Based on these data, TCERG1 has been suggested to couple the transcribing RNA polymerase II (RNAPII) with spliceosome complexes to regulate co-transcriptional splicing events. We recently found support for this hypothesis by showing that TCERG1 regulated the alternative splicing of the BCL2L1 gene by modulating the rate of RNAPII transcription. Recently, we have identified and characterized the speckle-targeting signal of TCERG1 that might participate in the coordination of transcription and splicing. In an effort to investigate the mechanism of TCERG1 recruitment to active processing sites, we identified a nuclear protein that specifically interacts with the speckle-nuclear localization signal of TCERG1. Surprisingly, this protein was NOLC1, a nucleolar phosphoprotein that shuttles between the nucleolus and the Cajal body, which have been implicated in the biogenesis of the small nuclear ribonucleoproteins (snRNPs) to form the spliceosome. Here, we present data concerning the biochemical characterization of this novel interaction, the requirement of TCERG1 for correct Cajal body formation, and the involvement of TCERG1 in regulating snRNPs biogenesis. Our studies provide new insights into the spatial organization and dynamics of transcription and pre-mRNA processing within the highly compartmentalized eukaryotic nucleus, which are fundamental to fully understand how the regulation of gene expression is exerted in the cell.