Transcriptional Coactivator PGC-1α Binding to Newly Synthesized RNA via CBP80: A Nexus for Co- and Posttranscriptional Gene Regulation

Abstract

Mammalian cells have many quality-control mechanisms that regulate protein-coding gene expression to ensure proper transcript synthesis, processing, and translation. Should a step in transcript metabolism fail to fulfill requisite spatial, temporal, or structural criteria, including the proper acquisition of RNA-binding proteins, then that step will halt, fail to proceed to the next step, and ultimately result in transcript degradation. Quality-control mechanisms constitute a continuum of processes that initiate in the nucleus and extend to the cytoplasm. Here, we present published and unpublished data for protein-coding genes whose expression is activated by the transcriptional coactivator PGC-1α. We show that PGC-1α movement from chromatin, to which it is recruited by DNA-binding proteins, to CBP80 at the 5′ cap of nascent transcripts begins a series of co- and posttranscriptional quality- and quantity-control steps that, in total, ensure proper gene expression.