April 20, 2002 | David F. Coppedge

Your Inner Postal Service

51; Zip codes – those five- or nine-digit numbers on mail – have an analogue in every one of your cells.  Like a city,1 a cell has information to ship from place to place.2  To make sure that the manufacturing instructions for protein parts arrive at the appropriate assembly site, the shipper puts a molecular tag on a transport vehicle (the postman) that works just like a zip code.  At least that is the way an article in PLoS Biology described the process.
    Richard Robinson is a freelance science writer who wrote in the peer-reviewed, open-access science journal PLoS Biology about “A Two-Step Process Gets mRNA Loaded and Ready to Go.”3  (mRNA refers to the messenger RNA, the edited transcript of DNA, that contains the coded instructions for a protein.)  He used the word “zipcode” five times in his description of recent findings about the process:

Proteins are the workhorses of the cell, but to get the most work out of them, they need to be in the right place.  In neurons, for example, proteins needed at axons differ from those needed at dendrites, while in budding yeast cells, the daughter cell needs proteins the mother cell does not.  In each case, one strategy for making sure a protein gets where it belongs is to shuttle its messenger RNA to the right spot before translating it.
    The destination for such an mRNA is encoded in a set of so-called “zipcode” elements, which loop out of the RNA string to link up with RNA-binding proteins.  In yeast, these proteins join up with a myosin motor that taxis the complex to the encoded location.

The players in this process are the messenger RNA (mRNA) with the coded instructions (like blueprints) for a molecular machine, the zipcode elements attached to the mRNA that tell it where it needs to go, and the myosin “taxi” that takes the mRNA to the right factory (ribosome) where the protein parts will be assembled.  But other parts must be involved; who sorts the mail?  Who checks that the zip code is present?
    The rest of Robinson’s synopsis discussed how recent findings show more complexity than previously known (see 06/26/2002, 09/06/2002, 01/01/2005, 01/13/2007).  It was known that proteins called She2p and She3p were involved, but not how they interacted with the zipcode elements on the mRNA.  There is a new level of quality control, he said, that has come to light:

Based on their results, the authors propose a two-step model of transport complex formation.  Within the nucleus, She2p binds to the mRNA as it is transcribed, and then shuttles it to the cytoplasm.  She2p binds loosely and promiscuously, though, catching up mRNAs both with and without zipcodes.  Once in the cytoplasm, She3p joins on, tightening the grip on mRNAs that contain zipcodes while booting out those without them.  With the myosin motor attached to She3p, the complex motors off to its destination elsewhere in the cell.
    The results in this study indicate that quality control in mRNA transport relies on a reciprocal action: the complex proteins together ensure that only those mRNAs with a destination tag are incorporated into the transport complex, and the mRNA, by binding to each of the proteins in the complex, ensures that all are on board before the journey starts.

In other words, one protein (She2p) binds to the parcel inside the nucleus and takes it outside, where the other protein (She3p) recognizes its counterpart, checks the zipcode, and joins the transport complex to the myosin taxi.  Studies have shown that without this quality-control mechanism, like when She2p mutated to prevent it joining with the mRNA, “the ability of the RNA�protein complex to reach its destination was impaired.”
    Robinson’s comments referred to a paper by Muller et al in PLoS Biology.4  The authors stated, “We propose that coupling of specific mRNA recognition and assembly of stable transport complexes constitutes a critical quality control step to ensure that only target mRNAs are transported.”  They also used the phrase “zip code” 68 times, but never mentioned evolution once, except obliquely in one figure, to show phylogenetic comparisons of She3p between different species of yeast.


1.  Michael Denton compared the cell to a city in a memorable chapter of his 1985 book, Evolution: A Theory in Crisis, p. 328.  His description began, “To grasp the reality of life as it has been revealed by molecular biology, we must magnify a cell a thousand million times until it is twenty kilometres in diameter and resembles a giant airship large enough to cover a great city like London or New York.  What we would then see would be an object of unparalleled complexity and adaptive design…. a world of supreme technology and bewildering complexity.”
2.  Ibid., “A huge range of products and raw materials and raw materials would shuttle along all the manifold conduits in a highly ordered fashion to and from all the various assembly plants in the outer regions of the cell.”
3.  Richard Robinson, “A Two-Step Process Gets mRNA Loaded and Ready to Go,” Public Library of Science: Biology, 9(4): e1001047. doi:10.1371/journal.pbio.1001047.
4.  M�ller M, Gerhard Heym R, Mayer A, Kramer K, Schmid M, et al. (2011), “A Cytoplasmic Complex Mediates Specific mRNA Recognition and Localization in Yeast,” doi:10.1371/journal.pbio.1000611.

The guys who make up stories about life originating from primordial soup don’t think of any of these things.  They get all excited if they find a strand of RNA that can make one simple chemical reaction occur, as if that’s all that is needed.  But give them the best case scenario: a primitive cell filled with the essential molecules of life, but no process for getting the molecules where they are needed.  That includes no quality control, no inspections, no checks and balances, no feedback, no networks.  What will happen?  Entropy.
    We remind our readers that evolutionary theory provided nothing to this scientific discovery.  We also remind them that these complex processes were described not for the most complicated eukaryotes, like giraffes, but ones much more humble: yeast.

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