Abstract
In eukaryotic cells, most mRNAs are exported from the nucleus by the transcription export (TREX) complex, which is loaded onto mRNAs after their splicing and capping. We have studied in mammalian cells the nuclear export of mRNAs that code for secretory proteins, which are targeted to the endoplasmic reticulum membrane by hydrophobic signal sequences. The mRNAs were injected into the nucleus or synthesized from injected or transfected DNA, and their export was followed by fluorescent in situ hybridization. We made the surprising observation that the signal sequence coding region (SSCR) can serve as a nuclear export signal of an mRNA that lacks an intron or functional cap. Even the export of an intron-containing natural mRNA was enhanced by its SSCR. Like conventional export, the SSCR-dependent pathway required the factor TAP, but depletion of the TREX components had only moderate effects. The SSCR export signal appears to be characterized in vertebrates by a low content of adenines, as demonstrated by genome-wide sequence analysis and by the inhibitory effect of silent adenine mutations in SSCRs. The discovery of an SSCR-mediated pathway explains the previously noted amino acid bias in signal sequences and suggests a link between nuclear export and membrane targeting of mRNAs.
Highlights
In eukaryotes, messenger RNAs (mRNAs) are synthesized and processed in the nucleus before they are transported through the nuclear pores into the cytoplasm, where they are translated into proteins
Nuclear export of most mRNAs is mediated by the conserved transcription export (TREX) complex that is comprised of the Tho complex, UAP56, and Aly
The resulting mature mRNA is exported from the nucleus to the cytoplasm by crossing the nuclear pore. Both the introns and the cap help to recruit factors that are necessary for nuclear export of an mRNA
Summary
MRNAs are synthesized and processed in the nucleus before they are transported through the nuclear pores into the cytoplasm, where they are translated into proteins. TAP interacts with nucleoporins directly [7,8,9] or through the factor Rae1 [10,11] and may allow bound transcripts to enter and eventually pass through the nuclear pores. It remains unclear how mRNAs exit the pores on the cytoplasmic side, but RNA helicases, such as Dbp, may be involved [12,13]. Many details of the export mechanism remain to be clarified, it seems clear that the efficient export of most mRNAs requires both splicing and a functional cap
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