Abstract:
Pre-mRNA is transcribed primarily from genes located at the interface between chromatin domains and the interchromatin space. After partial or complete processing and complexing with nuclear proteins, the transcripts leave their site of synthesis and travel through the interchromatin space to the nuclear pores for export to the cytoplasm. It is unclear whether transcripts are tethered within the interchromatin space and move toward the nuclear pores using a metabolic energy-requiring, directed mechanism or, alternatively, move randomly by a diffusion-based process. We discuss here recent progress in understanding this step of gene expression, including our experiments tracking the movement of intranuclear poly(A) RNA in living cells. Our results and those of others are most consistent with a model in which newly synthesized mRNAs diffuse throughout the interchromatin space until they randomly encounter and are captured by the export machinery. Because the export machinery appears to preferentially bind transport-competent mRNAs (complexed with the correct complement of nuclear proteins), this diffusion-based model for intranuclear RNA movement potentially allows for a significant level of posttranscriptional control of gene expression.