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C. Guthrie, B. Patterson, "Spliceosomal snRNAs," Annual Review of Genetics, 22, 387-419, 1988. Bruce Patterson (University of California, San Francisco): "Carl Woese [The Scientist, May 14, 1990, page 22] and Harry Noller pioneered the `phylogenetic approach' to rRNA structure/function, reasoning that highly conserved features of an RNA reflect functionally important domains or moieties (C.R. Woese, Microbiol. Rev., 51:221-71, 1987; H.F. Noller, Ann. Rev. Biochem., 53:119-62, 1984). We wrote our paper to make an snRNA sequence compilation available to the splicing field and to summarize current knowledge about the identified functions of conserved sequences. This represents a starting point for the making and breaking of models of snRNA structure and function. By examining the consensus lines, one can tap into millions of years of mutation filtered through natural selection. Seeing what alternatives are successful targets specific regions for contemplation or mutagenesis, obviating brute-force approaches. Further, a popular game in the RNA world is the spontaneous generation of models, which propose interactions between different snRNAs based on possible Watson-Crick base pairings. When one adds the constraint of conservation in the half-dozen distantly related sequences, a given model instantly becomes intriguing or historical. Putting this paper together was a grotesquely tedious chore, but apparently a timely one." A.J. Courey, R. Tjian, "Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif," Cell, 55, 887-98, 2 December 1988. Albert J. Courey (University of California, Berkeley): "As one of the earliest known eukaryotic promoter-selective transcription factors, Sp1 has been the subject of intense investigation in a number of laboratories around the world. This article reports the use of a Drosophila tissue-culture cell cotransfection assay to analyze the relationship between the structure and function of this factor. We found that Sp1 contains multiple transcriptional activation domains, the two most potent of which are characterized by a high content of glutamine residues and a low density of charged residues. These glutamine-rich regions appear to represent a new class of activation domains distinct from the acidic activation domains previously characterized in other factors. Interestingly, a number of regulatory proteins, including Oct1, Oct2, and a variety of proteins controlling Drosophila development, contain glutamine-rich regions, which may play roles in transcriptional regulation. Recent experiments support the notion that these diverse glutamine-rich regions are indeed capable of serving as activation domains." S.G. Rhee, P.-G. Suh, S.-H. Ryu, S.Y. Lee, "Studies of inositol phospholipid-specific phospholipase C," Science, 244, 546-50, 5 May 1989. Sue Goo Rhee (National Heart, Lung, and Blood Institute, Bethesda, Md.): "Inositol phospholipid-specific phospholipase C (PLC) is the enzyme that generates phosphoinositide-derived second messenger molecules when hormones, growth factors, and neurotransmitters bind to specific receptors on the external surface of a cell. These second messengers evoke a host of intracellular reactions that lead to many cellular processes. This review describes four immunologically distinct PLC isozymes that are quite dissimilar, not only in molecular size but also in amino acid sequence. They are expressed differently between tissues and between individual cells during development. These results suggest that each isozyme is coupled to a different receptor and regulated by different means. Our observation raises the possibility that each PLC isozyme can be a target for a new generation of drugs, which is specific to tissues and cell types." D.B. Pritchett, H. Sontheimer, B.D. Shivers, S. Ymer, H. Kettenmann, P.R. Schofield, P.H. Seeburg, "Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology," Nature, 338, 582-5, 13 April 1989. Peter H. Seeburg (University of Heidelberg, W.Ger.): "Our work gives currency to the notion that recombinantly expressed GABAA receptors can indeed mimic the properties of cognate receptors in the central nervous system. For a time, molecular neuropharmacologists were unable to re-create the high-affinity binding site for benzodiazepines in vitro, using cloned components of the GABAA receptor complex. We found the missing piece of the molecular puzzle in the form of a novel receptor subunit, which we call ç. Understanding the makeup of this site is of eminent interest to many researchers in clinical pharmacology, molecular neurobiology, and the pharmaceutical industry. Our findings open the door to the construction of molecular screening systems for facilitating the design and fine-tuning of novel drugs that act with specificity on any one of the numerous GABAA receptor subtypes, the key components in the fast signal transmission of our brain." PHYSICS M. Böttiker, "Absence of backscattering in the quantum Hall effect in multiprobe conductors," Physical Review B, 38, 9375-89, 15 November 1988. Markus Böttiker (IBM Thomas J. Watson Research Center, Yorktown Heights, N.Y.): "Eight years after the discovery of the quantum Hall effect, my paper presented a transport theory, which is particularly close to the setup actually used to measure the effect. Earlier theories that stressed the topological nature suggested that the quantum Hall effect is largely independent of the properties of the sample. In contrast, my discussion showed that the properties of the current source contact and current sink contact and the properties of the contacts used to measure voltages are of importance for the quantization of the resistance. Fortunately, since the publication of my paper, a number of groups from different parts of the world have carried out experiments that confirm my predictions. Most exciting, it was since discovered that the nonlocal effects that give rise to deviations from the quantum Hall effect persist over macroscopic distances."

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