Export and stability of naturally intronless mRNAs require specific coding region sequences and the TREX mRNA export complex.

A great deal is known about the export of spliced mRNAs, but little is known about the export of mRNAs encoded by human cellular genes that naturally lack introns. Here, we investigated the requirements for export of three naturally intronless mRNAs (HSPB3, IFN-α1, and IFN-β1). Significantly, we found that all three mRNAs are stable and accumulate in the cytoplasm, whereas size-matched random RNAs are unstable and detected only in the nucleus. A portion of the coding region confers this stability and cytoplasmic localization on the naturally intronless mRNAs and a cDNA transcript, which is normally retained in the nucleus and degraded. A polyadenylation signal, TREX mRNA export components, and the mRNA export receptor TAP are required for accumulation of the naturally intronless mRNAs in the cytoplasm. We conclude that naturally intronless mRNAs contain specific sequences that result in efficient packaging into the TREX mRNA export complex, thereby supplanting the splicing requirement for efficient mRNA export.