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About the Cover

Cover Figure


Cover   The belief that RNA was copied from DNA in strictly linear fashion was deeply ingrained and underpinned the understanding of gene expression prior to 1977. This was so much so that the discovery celebrated in this month's cover of Molecular Biology of the Cell was marked by one landmark paper entitled "An Amazing Sequence Arrangement at the 5' Ends of Adenovirus 2 Messenger RNA." This paper, by Louise Chow, Richard Gelinas, Thomas Broker, and Richard Roberts (Cell 12, 1-18, 1977), and that of Susan Berget, Claire Moore, and Philip Sharp of the same year (Proc. Natl. Acad. Sci. USA 74, 3171-3175, 1977), described the first evidence for splicing of premessenger RNA: that occurring in the viral mRNAs of adenovirus-infected cells. By a clever combination of electron microscopic and other mapping methods, it was found that the 5' leader sequences of adenoviral major late mRNAs, upstream of their translated portions, were actually derived from no less than three widely spaced regions of the adenoviral genome. It had been clear that tRNAs and some ribosomal RNAs also contained intervening sequences, but not whether these constituted special cases that would not extrapolate to the protein-coding mRNAs. In the cover photograph, the technique of electron microscopy is applied to hybridized stretches of viral genomic DNA and mRNA. Such visualization was especially visually striking in conveying the "message" of a completely new phenomenon that broke away from the then-current paradigms about linearity of the genetic information. Loops were seen, such as the one below and left of the center of this electron micrograph, that were not just the long flexible nucleic acid chain crossing its previous path on the electron microscope grid surface. Instead, they were fixed in length and resulted from different regions of genomic DNA being brought into close proximity by the spliced regions, and therefore now neighboring regions, of mRNA. Electron microscopy of mRNA-gene DNA hybrids by Shirley Tilghman, David Tiemeyer, John Seidman, Matija Paterlin, Margery Sullivan, Jacob Maizel, and Philip Leder provided compelling visualization of the fact that a cellular gene, a globin gene, consisted of three noncontiguous segments that were joined into the mature mRNA by a "bighting-ligating" reaction, as they dubbed it in their paper in Proc. Natl. Acad. Sci. USA 75, 725-729, 1978. This showed that the unexpected phenomenon extended to cellular RNA and to the protein-coding mRNA sequences themselves. Further explorations that were started by these findings have led over the past 20 years to a number of completely new views of cellular processes. These include the complexity of the steps required before the genetic information in eukaryotic cells eventually gets to the translational machinery, findings about the involvement of RNA in splicing that are key to the "RNA world" hypothesis, and a growing appreciation of how many processes in the cell nucleus are functionally integrated. ---Elizabeth Blackburn Cover figure reprinted with the permission of Cell Press.


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