Secrets of the Spliceosome Revealed
A husband and wife team from Hebrew University has revealed the structure of the spliceosome, one of the most complex molecular machines in the cell (see 09/12/2002 headline), in more detail than ever before, says EurekAlert. The spliceosome is responsible for cutting out the introns in messenger RNA after it has transcribed DNA, and also for “alternative splicing” that rearranges the exons to produce a variety of proteins from the same DNA template: “Alternative splicing, which underlies the huge diversity of proteins in the body by allowing segments of the genetic code to be strung together in different ways, takes place in the spliceosome as well.”
The Sperlings found a tunnel between the two major subunits of the machine where they believe the cutting and splicing operations take place, and also a cavity that might provide a safe haven for the messenger RNA strand, like a waiting room, before its surgery. Also, they found that four spliceosomes are bound together into a “supraspliceosome” which is able to do “simultaneous multiple interactions, rather than by a stepwise assembly” as inferred from other experiments in vitro. Their investigation in vivo (within a functioning, living cell) revealed even more complexity in the composite machine than had been seen in the individual machines:
Such a large number of interactions that the cell has to deal with can be regulated within the supraspliceosome. Having the native spliceosomes as the building blocks of this large macromolecular assembly, this large number of interactions can be compartmentalized into each intron that is being processed. At the same time, the whole supraspliceosome enables the communication between the native spliceosomes, which is needed for regulated splicing. The organization of the supraspliceosome, like other macromolecular assemblies that exist as preformed entities, avoids the necessity to recruit the multitude of splicing components each time the spliceosome turns over. In that sense, the overall coordination of the cellular interactions is reduced from the hard work of repeatedly placing each piece in the correct position of the puzzle to the relatively simpler work of coordinating the preformed puzzle. (Emphasis added in all quotes.)
In short, “The supraspliceosome represents a stand-alone complete macromolecular machine capable of performing splicing of every pre-mRNA independent of its length or number of introns.” They found that the individual spliceosomes are joined with a flexible joint like a hinge to provide flexible interactions and communication. Their work was published in Molecular Cell Sept. 10.1
1Sperling et al., “Three-Dimensional Structure of the Native Spliceosome by Cryo-Electron Microscopy,” Molecular Cell, Volume 15, Issue 5, 10 September 2004, Pages 833-839; doi:10.1016/j.molcel.2004.07.022.
Can’t get enough of these molecular machines. And can’t repeat often enough that the more detail a scientific paper reveals about the complex workings inside the cell, the less they have to say about evolution. Quiz: how many times was evolution mentioned in this paper? Answer: zilch, zero, nada. They didn’t even say, “watch this space.” (see 09/08/2004 commentary).