The Half Decent Pharmaceutical Chemistry Blog

Back in the seventies, biologist Maurice Sussman must have been pretty fond of that pretty famous British band, The Beatles, to postulate a ”ticket-to-ride” hypothesis to explain the difference in length of the 3’-end between nuclear and cytoplasmic mRNAs.

Although this theory was proved wrong, I’ve decided to dedicate a post to it on my blog for two excellent reasons: first, because a group such as the Beatles deserves at least to be mentioned on my site. Then, because I like Sussman’s hypothesis very much: it's a bright example of creativity and taste for good music. And I think this is all that counts, after all.

Now, the back (3’-end) of a mature mRNA looks pretty much like this picture I drew in a coffee break: with a tail of approximately 250 adenines.

Once this mature transcript exits the nucleus, it gets translated. Then, the transcript remains in the cytoplasm and, little by little, while still ready for further cycles of translation, its tail starts to be shortened by something. Once this structure is entirely gone, the mRNA approaches the conclusion of its task.

Five years after the release of  “Ticket to Ride”, Sussman came up with this: once the yellow submarine…oh, sorry, mRNA has left the nucleus, its polyadenylated 3’-end serves as a (multiple) ticket for being translated: at every translation the ticket is punched, by cutting off a bit of adenines.
So, after a certain amount of cycles, the mRNA hasn’t got any more tickets and has to “get off”.

Sadly, this is not true, as researchers subsequently proved by measuring the rate of shortening of poly(A)s when a translation inhibitor, Emetine, was added: there’s almost no difference with the normal rate, assayed with translation underway, so, there’s no relationship between translating and shortening.

Moreover, after this early work, it became clear that the poly(A) tail isn’t just cut off: instead, a proper turn over is in place, with a cytoplasmic version of the PAP (Poly(A) polymerase) that adds a bit of adenines, whereas RNases degrade this structure.

This mechanism has its limits: after a certain amount of time, in fact, the polymerase succumbs to the efficient RNase, which works faster and, for each cycle, removes more adenines than those the cytoplasmic polymerase can add.

Still, you’ll agree with me that the ticket theory remains fascinating, won’t you?