TPR is required for the nuclear export of mRNAs and lncRNAs from intronless 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 nuclear export of mRNAs and lncRNAs that are generated from intronless and intron-poor genes, and we validate this with reporter constructs. Moreover, in TPRdepleted cells reporter mRNAs generated from intronless genes 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 required for the nuclear export of intronless and intron-poor mRNAs and lncRNAs.

GC‐content biases in protein‐coding genes act as an “mRNA identity” feature for nuclear export

“…The Ulitsky group also examined how mRNA export was affected by the depletion of TPR, the major component of the nuclear pore basket. In line with what our group previously documented, [ 61 ] they found that TPR was required for the export of intron‐poor mRNAs. These observations suggest that TPR and NXF1 may work together in a pathway that is separate from TREX.…”

“…These junk RNAs are thus retained in the nucleus and targeted for decay. Of course many lncRNAs that function in the cytoplasm, such as NORAD , [ 10,61,62 ] may use GC‐content to acquire export factors as well. It should also be noted that not all GC‐rich regions are created equal.…”

Distinct effects on mRNA export factor GANP underlie neurological disease phenotypes and alter gene expression depending on intron content

“…Whereas it is known that intron-containing genes are surveyed by quality control mechanisms to ensure that unspliced mRNAs are not exported (17), the export mechanisms of intronless genes have not been investigated in great detail. TREX has been suggested to be involved in export of intronless mRNAs in HeLa cells (33), NXF1/TAP pathway in exporting intronless histone H2A mRNA (34) and nuclear pore basket protein TPR in export of intronless transcripts (35). ATXN7L3B was one of the downregulated intronless genes in patients' cells where RNA in situ hybridization showed a reduction in its overall amount but no change in mRNA localization and no evidence for nuclear retention.…”

MKRN2 Physically Interacts with GLE1 to Regulate mRNA Export and Zebrafish Retinal Development

“…Cell Fractionation and RNA Seq Cell fractionation and RNA seq were performed essentially as described in Lee et al (2019), with minor modifications. 1 3 150mm dish of HEK293 Flp-In-TReX cells were depleted of MKRN2 for 5 days.…”