Wonders of the Spliceosome Coming to Light

The more we learn about a vital molecular machine in the nucleus, the spliceosome, the more complex and important it seems.

The spliceosome is a large “slicer and dicer” that takes DNA transcripts (messenger RNA) and prepares them for export out of the nucleus, where they will be translated into proteins.  Science Daily described what molecular biologists have learned about this amazing multi-function machine:

The process of splicing is carried out by a highly complex molecular machine termed the spliceosome. Human spliceosomes are built up from protein and RNA molecules. They contain some 170 different proteins and five RNA molecules termed “small nuclear RNAs” (snRNAs). It is currently believed that certain snRNAs represent the tools with which the spliceosome carries out the cutting and joining of RNA sections, turning the messenger RNA’s precursor (“pre‑mRNA”) into mature messenger RNA. The proteins of the spliceosome are needed to bring these tools to the right place at the right time, and to set them into operation. Splicing processes in higher organisms are very highly regulated. In fact, differing patterns of excision and joining of a given pre‑mRNA molecule can lead to any one of a selection of different mature mRNA molecules — all from the same gene. This ability to select the mRNA product according to need is termed “alternative splicing,” and it is thought to be the most important means by which human cells manage to produce a vast spectrum of different proteins from a relatively restricted number of protein-encoding genes.

So far, we’ve seen precision tools that arrive at precision times to do precision jobs.  We’ve seen that this multi-part, complex machine, aided by multiple other proteins and small RNA molecules, is capable of turning a transcribed gene into a vast array of protein templates by means of alternative splicing.  Years ago, it seemed a mystery why genes contained many apparently useless regions of code, dubbed introns, that had to be cut out of the messenger RNA (see 9/03/2003).  The spliceosome’s magic of alternative splicing is providing clues.

The article, based on a press release from the Free University of Berlin, used some pithy analogies to help readers understand the process.  One of the tools was likened to a knife in a sheath, that safely moves to the cutting site, waits for a “start signal,” then unsheathes itself and goes to work.  The start signal is given by another machine with a “remarkable molecular architecture” that enables the knife.  But that start-signal machine is held on a short leash by another machine, preventing it from giving the start signal.  That machine acts like a “plug in a stopper,” the researchers said, making sure the start signal is only given at the right time.

But then, the researchers found another machine that works in tandem with the “plug,” regulating the “start signal” independently.  “The existence of two or more different mechanisms to regulate the same cellular process underlines the importance of the exact timing of this process for the overall process of RNA splicing,” one of the researchers said.

This information is not just academic.  “In humans, errors in this control mechanism can lead to blindness.”  Could this machine have evolved by chance?  The article does not mention evolution.  It did say, though, that the spliceosome has some 170 different proteins.  Could chance build just one protein?  (See our online book for the unforgettable answer.)

We in this century are so privileged to get glimpses into the inner workings of life at its most basic level.  What would Aristotle or Galen, Leeuwenhoek or Darwin, thought if they knew that machinery—cutting tools, stoppers, regulators and other moving parts—so tiny as to be invisible without highly sophisticated human machinery—were keeping us alive?  Every second, every minute we are being upheld by trillions of machines like this that nobody even suspected were possible till the age of molecular biology.

Had Darwin known this, he might never have dared to write a story that blind, unguided processes could explain life.  There’s an interesting novella on that theme that was recently presented on ID the Future in audio format, 5 episodes.  “I, Charles Darwin” transports the bearded buddha into the 21st century, where he learns about these wonders and responds to them.  To encourage you to listen, we won’t spoil the end of the story.