REVIEWS
mRNA LOCALIZATION: MESSAGE ON THE MOVE Ralf-Peter Jansen Cytoplasmic messenger RNA localization is a key post-transcriptional mechanism of establishing spatially restricted protein synthesis. The characterization of cis-acting signals within localized mRNAs, and the identification of trans-acting factors that recognize these signals, has opened avenues towards identifying the machinery and mechanisms involved in mRNA transport and localization.
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany. e-mail: r.jansen@mail.zmbh.uniheidelberg.de
A key feature of eukaryotic cells is their organization into distinct compartments, each with a distinct set of proteins. Many student’s textbooks give the impression that sorting of proteins is mainly a post-translational event. Most proteins that are imported or integrated into organelles are, indeed, targeted to their destination on the basis of signals in the peptide sequence. But the past 15 years have shown that the sorting of several (mainly cytoplasmic) proteins involves an additional mechanism — messenger RNA localization. mRNA localization is a universal mechanism, with more than 90 localized mRNAs known so far. Most of these are found in oocytes and early embryos1; more than 20 are known in Drosophila melanogaster oocytes or embryos, and over 25 have been found in Xenopus laevis oocytes. The number of localized mRNAs detected in somatic cells is also increasing, with the dendritic compartment of neurons having been shown to accumulate a wealth of localized transcripts2. As well as transporting mRNA during oogenesis and targeting intracellular transcripts in somatic cells, plants seem to transport mRNAs over long distances through their vascular system3. And mRNA localization has been detected in single-celled organisms such as yeast4–6 and protozoa7. Progress has recently been made towards a detailed understanding of mRNA transport mechanisms. Some proteins that recognize localized mRNAs are now thought to assemble with the mRNA inside the nucleus, thereby ‘tagging’ the mRNA for subsequent recognition by the cytoplasmic transport apparatus. We know that cytoplasmic mRNA transport occurs in the form of large ribonucleoprotein (RNP) complexes, which might
contain a large number of mRNAs and proteins. And, finally, with the purification of large RNP complexes we should be able to identify their individual components. Biological function of mRNA localization
Why do cells localize mRNAs? Sometimes mRNA localization might be preferable to protein localization. Because one mRNA molecule can serve as a template for multiple rounds of translation, localizing mRNA rather than protein to the site where the protein is needed is obviously more energy efficient. In addition, there is a special requirement for high local levels of proteins that act as determinants to induce specific cell fates8. The synthesis of these cell-fate determinants must be restricted to defined cytoplasmic positions, as their mislocalization would be disastrous for the cell9,10. Examples of such cell-fate determinants include the products of the ASH1 gene in yeast, and the bicoid (bcd), nanos (nos) and oskar (osk) genes in Drosophila. mRNA localization might also be involved in the cotranslational assembly of supermolecular structures11. Some cytoskeletal proteins assemble, at least in part, during translation as nascent peptides12,13, and co-translational assembly would be facilitated by co-localization of the corresponding mRNAs. Co-translational assembly might explain why several transcripts co-localize in Naegleria, a single-celled protozoan that can switch between amoeboid and motile states. Upon the transition from the amoeboid to the flagellar states, localization of mRNAs encoding proteins of the microtubule cytoskeleton precedes assembly of the basal body, the microtubule-organizing centre7.
NATURE REVIEWS | MOLECUL AR CELL BIOLOGY
VOLUME 2 | APRIL 2001 | 2 4 7
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