TPR is required for the efficient nuclear export of mRNAs and lncRNAs from short and intron-poor genes

Abstract

While splicing has been shown to enhance nuclear export, it has remained unclear whether mRNAs generated from intronless genes use specific machinery to promote their export. Here, we investigate the role of the major nuclear pore basket protein, TPR, in regulating mRNA and lncRNA nuclear export in human cells. By sequencing mRNA from the nucleus and cytosol of control and TPR-depleted cells, we provide evidence that TPR is required for the efficient nuclear export of mRNAs and lncRNAs that are generated from short transcripts that tend to have few introns, and we validate this with reporter constructs. Moreover, in TPR-depleted cells reporter mRNAs generated from short transcripts accumulate in nuclear speckles and are bound to Nxf1. These observations suggest that TPR acts downstream of Nxf1 recruitment and may allow mRNAs to leave nuclear speckles and properly dock with the nuclear pore. In summary, our study provides one of the first examples of a factor that is specifically required for the nuclear export of intronless and intron-poor mRNAs and lncRNAs.