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Cell Biology
Case Made for Nuclear Export License
An unprecedented link between two fundamental mechanisms of the cell has been discovered by HMS researchers. Writing in the Sept. 21
Nature, Robin Reed, HMS professor of cell biology, and colleagues Zhaolan Zhou and Ming-juan Luo show for the first time that the protein Aly connects the splicing of pre-messenger RNA in the cell nucleus with the export of spliced messenger RNA to the cytoplasm. Aly is the counterpart in mammals of a known nuclear export factor in yeast, raising the likelihood that this link is highly conserved, or common to animals from the single-celled yeasts to mammals including humans, according to Reed.
The protein Aly seems to bridge the splicing and export processes of RNA: From top to bottom, the spliceosome assembles to edit pre-messenger RNA by cutting out the nonreading introns and splicing together the reading exons. Stored in nuclear speckles with other spliceosomal parts, Aly is recruited, becomes tightly associated with the now spliced mRNP, and is exported with the mRNP into the cytoplasm. Then Aly shuttles back to the speckles.
The Reed lab found that Aly is recruited to the spliceosome, a dynamic complex of proteins in the nucleus that splices pre-messenger RNA, the transcribed form of DNA. The spliceosome cuts out the introns, the long "junk," or noncoding, portions of RNA, and splices together the exons, the working instructions, into a messenger RNA protein complex called the mRNP. The researchers found that Aly tightly associates with the mRNP and may act as a kind of molecular stamp that says, in effect, these spliced exons are safe for export. The introns, meantime, are retained in the nucleus and degraded. The Aly-tagged mRNP is exported to the cytoplasm and translated into protein. Aly then shuttles back to the nucleus where it concentrates in local regions, dubbed speckles, that hold the spliceosome's many molecular parts.
Robin Reed (left) takes a break from RNA processing with Ming-juan Luo and Zhaolan Zhou (while Aly the Alligator lurks behind them). Photo by Steve Gilbert
A direct link between the spliceosome and the nuclear export mechanism had never been found until Aly. "It's recruited to the spliceosome and tightly associated with the mRNP, and Aly is also the first example of a protein that specifically stimulates the export of mRNA," said Reed. "This bridges the two different processes, so you have splicing on the one hand and export on the other and then this factor, Aly, links these two together because it has properties common to both."
