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Messenger RNA Localization In Yeast Yields New Clues On Development

Albert Einstein College of Medicine

The development of a complex organism from a single cell requires the establishment of daughter cells with different gene expression programs. it has been known for some time that such differential gene expression in the earliest-stage embryos of complex creatures such as drosophila is mediated, at least in part, by the localization of messenger RNA (mRNA) coding for gene-control proteins. Now new research from the laboratory of Robert Singer at the Albert Einstein College of Medicine, published in the July 18 issue of Science, indicates that mRNA localization also can regulate differential gene expression in Saccharomyces cerevisiae, commonly know as Brewer's yeast. The existence of the phenomenon in a eukaryotic cell type as evolutionarily ancient as yeast implies that mRNA localization may be a fundamental mechanism of different gene regulation for development and other processes.

The paper, whose first author is postdoctoral fellow Roy Long, is published in the July 18 issue of Science. Long and his colleagues studied a yeast protein called ASH1. This protein plays a critical role in distinguishing "daughter" yeast cells from the mother cells from which they bud. This distinction between the two cells is fundamental: A mother cell can change its "mating type" while the daughter cell cannot. Members of the laboratory of Dr. Kim Nasmyth of the Austrian Research Institute of Molecule pathology, a co-author of the Science paper, had previously tracked this difference down to a negative gene control protein called ASH1, which the daughter cell possesses at a substantially higher level than the other cell does.

In the new paper, Long and colleagues report that the differential gene expression controlled by ASH1 is due to the localization of ASH1 mRNA, which is directed to the tip of the budding daughter cell. Long and his colleagues also report that the message's movement depends on components of the actin cytoskeleton, and that a myosin mother is involved in the transport. They also identified a special "zipcode" region on the messenger RNA that directs it to the proper place in the cell.

For the past decade, Singer and his colleagues have conducted pioneering research demonstrating that mRNA localization is an important mechanism by which the cells of higher organisms regulate cell structure and function. But the discovery of mRNA localization in yeast shows that the process was presented early in evolution and thus is a fundamental one. In fact, it may have played an important role in the regulation of development as higher, multicellular organisms evolved. The localization of mRNA in yeast may even give support to the notion that the earliest biotic world was an "RNA world"--one in which RNA, not DNA, performed all the cell's vital information-storage and regulatory roles, including the control of the expression of genetic instructions.

Moreover, when fundamental cellular mechanisms go awry, disease can often result. Indeed, the Singer group has already found that myotonic dystrophy, the most common form of adult muscular dystrophy, probably occurs because of a defect in RNA localization. Neurological diseases such as Alzheimer's Disease and schizophrenia have also been traced to the faulty migration of developing nerve cells, and these and other diseases may be due, at least in part, to the faulty localization of mRNAs responsible for neuronal movement.

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