Not all export-competent mRNA is actually sent out of the nucleus to the cytoplasm, where it can be translated. On page , Schmidt et al. present evidence that a large percentage of spliced, mature mRNA is retained in nuclear speckles.
The authors tracked the position of mature mRNAs in live cells using the bimolecular fluorescence complementation assay. In the authors' system, only transcripts that were bound to both the Y14 splicing factor and the NXF1 export factor produced a fluorescent signal, thus indicating specifically mRNAs that are spliced and ready for export. These complexes resided mostly within and around SC35-containing nuclear speckles, which are thought to be sites of RNA splicing.
Although already bound to at least part of the export machinery, roughly half of the mature spliced messages were nonetheless retained in speckles for hours, as shown by FRAP and FLIP analyses. The addition of ATP to permeabilized cells depleted the immobile fraction from the speckles.
The findings suggest that speckles prevent the export of otherwise fully processed mRNAs until an energy-requiring cellular signal releases them. Export, in addition to transcription and translation, is thus a regulated step controlling the levels of a given protein. The authors would now like to follow individual RNA species to determine what sorts of signals might be involved and whether such signals are general or message specific.
