SUMMARY | FULL STORY
CELL BIOLOGY
Protein Components Identified in RNA Splicer
Network Coordinates Steps of Gene Expression
The genomes of more complex organisms, which contain huge stretches of noncoding DNA, require extensive editing before their transcribed RNA products make sense as proteins. The editorial department overseeing this undertaking is the spliceosome, five RNA molecules surrounded by complexes of proteins that carry out the task of splicing out the noncoding introns from meaningful exons. An analysis of this complex, led by Robin Reed and published in the Sept. 12 Nature, captures for the first time the complete set of proteins in a functional human spliceosome.
With careful biochemical techniques and powerful proteomic tools, Zhaolan Zhou (left) and Robin Reed captured a complete set of proteins involved in RNA splicing. (Photo by Steve Gilbert)
Capturing a spliceosome in action has been a long-sought goal for Reed, HMS professor of cell biology. Since it is such a large complex of proteins, it has been difficult to isolate in its native environment. Reed and first author Zhaolan Zhou were able to develop a method of binding spliceosomes using beads that can be disengaged with maltose, a gentle sugar that leaves the complex intact and functional. With the precious sample in hand, Reed and Zhou then collaborated with Steven Gygi's mass spectrometry lab at HMS to determine the contents. This powerful proteomic tool has been winning the hearts of researchers at HMS for its ability to quickly characterize proteins even from large protein complexes that would have been impossible to study before.
A complex network of coupled interactions is involved in gene expression. The major steps of gene expression are shown at left, and to the right are the processes within each of these steps. The arrows indicate that evidence has been found for physical or functional coupling between two steps in the form of common coupling proteins. (Illustration by Jeff Cleary)
To the team's surprise, the mass spectrometer pulled out a whopping 145 proteins, much more than the 50 previously estimated. Many of the newfound members also share duties in other aspects of gene expression and might be serving as a link between splicing and other processes. Over the past few years, several groups have identified "coupling" proteins that are common to more than one stage of gene expression. Reed believes these individual examples of coupling suggest that these processes, often looked at as separate events, really are part of an integrated network coordinating gene expression.
--Courtney Humphries
Copyright 2002 by the President and Fellows of Harvard College
