Molecular Biology

T. Hai, F. Liu, W.J. Coukos, M.R. Green, "Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers," Genes and Development, 3, 2083-90, December 1989. Michael R. Green (University of Massachusetts Medical Center, Worcester, Mass.): "I suspect that this paper may have attracted more than the usual attention because it is relevant to several research areas, and some of the results were unexpected. We and others had been studying ATF [activating transcription factor] proteins because they play an essential role in adenovirus transcriptional regulation. Other laboratories, which focused on cellular genes, were also interested in ATF proteins, whose binding sites are present in many cellular promoters. All of the ATF proteins that we cloned contained leucine zippers, and could selectively heterodimerize, making them relevant to researchers contemplating leucine zipper interactions. Our cloning revealed a surprisingly large number of different activating transcription factor proteins. Although we were excited by this finding, my mood turned more sober as it became clear that this complexity enormously confounds the study of ATF protein function. It will be interesting to see how long it takes before we truly understand why eukaryotic transcription factors, such as ATF, come as families." M. Yanagisawa, T. Masaki, "Molecular biology and biochemistry of the endothelins," Trends in Pharmacological Sciences, 10, 374-8, September 1989. Tomoh Masaki (University of Tsukuba, Japan): "The novel peptide endothelin is a potent vasoconstrictive peptide that is produced by endothelial cells. The peptide is now in the limelight because of its unique structural and pharmacological properties. Following our discovery of the peptide in 1988 [M. Yanagisawa, et al., Nature, 332:411-5, 31 March 1988], an enormous worldwide research activity was evoked in this field. "The exact nature of endothelin is still to be determined, but the peptide is expected to play some roles in the maintenance of blood pressure and in some pathophysiological phenomena, such as hypertension and vasospasm. In addition, recent works suggest that the peptide plays some other role in nonvascular tissues, such as neuron or kidney. Probably future research on endothelin will be as important in these nonvascular tissue studies as it will be in studies of the vascular system." C.R.J. Bandziulis, M.S. Swanson, G. Dreyfuss, "RNA-binding proteins as developmental regulators," Genes and Development, 3, 431-7, April 1989. Gideon Dreyfuss (University of Pennsylvania School of Medicine, Philadelphia): "Protein structural comparisons led to the discovery of identifying and unifying features shared by RNA-binding proteins of the nucleus and cytoplasm, including pre-mRNA-, snRNA-, and pre-rRNA-binding proteins. Many of these ribonucleoproteins contain a RNA-binding domain (RBD) of approximately 90 amino acids. This amino acid sequence is conserved in organisms as diverse as yeast and humans. The most highly conserved motif within the RBD is an octapeptide, termed the ribonucleoprotein consensus sequence (RNP-CS), which is the identifying feature of this group of proteins. Frequently, these proteins contain several similar, but nonidentical, RBDs. In addition, all of these proteins contain at least one auxiliary domain, which is unique to each type of protein and which most likely functions in protein-protein interactions--a necessary feature, as many of the RNP proteins form multiprotein complexes. RNP-CS proteins display binding preferences for specific RNA sequences, and several have been shown to interact with pre-mRNA sequences important for pre-mRNA processing. "The consensus motif has been used by many investigators to assign a RNA-binding function to newly discovered proteins, and has built a quick bridge between the proteins that bind to the many different RNAs along the pathway of gene expression. Several groups have identified RNP-CS proteins in Drosophila melanogaster that are involved in controlling key developmental decisions through alternative pre-mRNA processing. It was not difficult to realize that this evidence pointed to RNP proteins as a new class of regulatory molecules in gene expression. "In this article we tried to provide an overview of the structural characteristics of RNP-CS proteins and speculate on how their modular structure may facilitate their participation in pathways that regulate development at the post-transcriptional level. We think the reason this article turned out to be of wide interest is that it brings together a variety of lines of investigation in molecular, cellular, and developmental biology and, we hope, harmonizes what were seemingly incongruous cellular events."

Molecular Biology

The Scientist Staff

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