Big Problems Faced in RNA Processing: The search for the secrets of splicing messenger RNA involves some steps forward and some back

R Lewin - Science, 1982 - science.org
R Lewin
Science, 1982science.org
Most RNA is synthesized as a precursor and must be processed before it can be active in
the cell. A multiplicity of cleavage, ligation, addition, and chemi-cal modification reactions
have been recognized as essential steps in the matura-tion of RNA, the most notorious of
which is the precise removal of noncod-ing, or intron, regions from the messenger RNA
molecules of higher organisms. The discovery of split genes, announced 5 years ago this
month, endowed the study of RNA processing with a glamor it previously lacked. It is now an …
Most RNA is synthesized as a precursor and must be processed before it can be active in the cell. A multiplicity of cleavage, ligation, addition, and chemi-cal modification reactions have been recognized as essential steps in the matura-tion of RNA, the most notorious of which is the precise removal of noncod-ing, or intron, regions from the messenger RNA molecules of higher organisms. The discovery of split genes, announced 5 years ago this month, endowed the study of RNA processing with a glamor it previously lacked. It is now an intense field of activity, and one recently discussed at a Cold Spring Harbor meeting at the end of May.
Although, alas, the processing of in-trons from messenger RNA remains virtually as much a mystery as it was 5 years ago, the meeting was impressed with two firm and important messages, one of which has fascinating implications for the study of the origin of life. First, while the primary sequence of RNA molecules is often essential for their function, it is now clear that the crucial dimension of activity is the ter-tiary structure." For the first time many people appreciated higher orderstructure inRNA," says Norman Pace of the National Jewish Hospital, Denver, Colorado." RNA is much more profound structurally thanDNA." Second, RNA is now known to be more than a simple passive molecular scaffold insome important instances. In combining with proteins, RNA might sometimes play a direct role in the me-chanics of a catalyzed reaction. And in one case of RNA processing so far dis-covered, an RNA molecule displays en-zymic activity in the total absence of protein." This discovery helps simplify our thinking about the components re-quired in the primordial replicating sys-tems," says Pace. It also demands that the chemistry of other RNA molecules be examined more closely to see how general this phenomenon might be. Beyond these broad conclusions, the Cold Spring Harbor meeting brought into sharp focus the key problems in RNA processing research. Specifically, these concern the physical nature of cellular
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