trans Regulation: Do mRNAs Have a Herd Mentality? (original) (raw)
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A translation-independent role of oskar RNA in early Drosophila oogenesis
Development, 2006
The Drosophila maternal effect gene oskar encodes the posterior determinant responsible for the formation of the posterior pole plasm in the egg, and thus of the abdomen and germline of the future fly. Previously identified oskar mutants give rise to offspring that lack both abdominal segments and a germline, thus defining the `posterior group phenotype'. Common to these classical oskar alleles is that they all produce significant amounts of oskar mRNA. By contrast, two new oskar mutants in which oskar RNA levels are strongly reduced or undetectable are sterile, because of an early arrest of oogenesis. This egg-less phenotype is complemented by oskar nonsense mutant alleles,as well as by oskar transgenes, the protein-coding capacities of which have been annulled. Moreover, we show that expression of the oskar 3′ untranslated region (3′UTR) is sufficient to rescue the egg-less defect of the RNA null mutant. Our analysis thus reveals an unexpected role for oskar RNA during early o...
Translational repressor bruno plays multiple roles in development and is widely conserved
Genes & Development, 1997
oskar (osk) mRNA is tightly localized to the posterior pole of the Drosophila oocyte, where the subsequent expression of Osk protein directs abdomen and germ-line formation in the developing embryo. Misplaced expression of Osk protein leads to lethal body patterning defects. The Osk message is translationally repressed before and during the localization process, ensuring that Osk protein is only expressed after the mRNA has reached the posterior. An ovarian protein, Bruno (Bru), has been implicated as a translational repressor of osk mRNA. Here we report the isolation of a cDNA encoding Bru using a novel approach to the expression cloning of an RNA-binding protein, and the identification of previously described mutants in the arrest (aret)-locus as mutants in Bru. The mutant phenotype, along with the binding properties of the protein and its pattern of accumulation within the oocyte, indicate that Bru regulates multiple mRNAs involved in female and male gametogenesis as well as early in embryogenesis. Genetic experiments provide further evidence that Bru functions in the translational repression of osk. Intriguingly, we find that Bru interacts physically with Vasa (Vas), an RNA helicase that is a positive regulator of osk translation. Bru belongs to an evolutionarily conserved family of genes, suggesting that Bru-mediated translational regulation may be widespread. Models for the molecular mechanism of Bru function are discussed.
RNA (New York, N.Y.), 2015
The Drosophila oskar (osk) mRNA is unusual in that it has both coding and noncoding functions. As an mRNA, osk encodes a protein required for embryonic patterning and germ cell formation. Independent of that function, the absence of osk mRNA disrupts formation of the karyosome and blocks progression through oogenesis. Here we show that loss of osk mRNA also affects the distribution of regulatory proteins, relaxing their association with large RNPs within the germline, and allowing them to accumulate in the somatic follicle cells. This and other noncoding functions of the osk mRNA are mediated by multiple sequence elements with distinct roles. One role, provided by numerous binding sites in two distinct regions of the osk 3' UTR, is to sequester the translational regulator Bruno (Bru), which itself controls translation of osk mRNA. This defines a novel regulatory circuit, with Bru restricting the activity of osk, and osk in turn restricting the activity of Bru. Other functional e...
Between transcription and translation: Redefining RNA and regulation
Fly, 2008
The diverse functional roles for RNA molecules in cells of the developing embryo have been an area of intense study in the last few years. Progress reported at the 49 th Annual Drosophila Research Conference in San Diego, California highlighted many of the varied mechanistic activities for RNAs. In particular, talks at the 'RNA Biology' platform session provided a great deal of insight into the function of RNA transcripts and their associated protein complexes. The topics covered included: (1) a large-scale screen examining the localization of mRNAs during embryonic development, (2) mechanisms of mRNA transport in different cell types, (3) localization-dependent repression of mRNA translation and (4) the activity of the RNAi machinery in insulator-mediated chromatin structures. Our journey through the modern RNA world clearly indicates that we should be considering a much more expansive role for RNAs in molecular biology.
Premature translation of oskar in oocytes lacking the RNA-binding protein bicaudal-C
Molecular and cellular biology, 1998
Bicaudal-C (Bic-C) is required during Drosophila melanogaster oogenesis for several processes, including anterior-posterior patterning. The gene encodes a protein with five copies of the KH domain, a motif found in a number of RNA-binding proteins. Using antibodies raised against the BIC-C protein, we show that multiple isoforms of the protein exist in ovaries and that the protein, like the RNA, accumulates in the developing oocyte early in oogenesis. BIC-C protein expressed in mammalian cells can bind RNA in vitro, and a point mutation in one of the KH domains that causes a strong Bic-C phenotype weakens this binding. In addition, oskar translation commences prior to posterior localization of oskar RNA in Bic-C- oocytes, indicating that Bic-C may regulate oskar translation during oogenesis.
Localization-Dependent Oskar Protein Accumulation
Developmental Cell, 2004
Biology with Cup, and cup mutants are defective in repression The University of Texas at Austin of osk mRNA translation (Nakamura et al., 2004; Wilhelm Austin, Texas 78712 et al., 2003). Cup also binds to translation initiation factor eIF4E, and in doing so prevents the interaction of eIF4E with eIF4G that is essential for cap-dependent transla-Summary tion (Nakamura et al., 2004; Nelson et al., 2004; Wilhelm et al., 2003). Although this model for the mechanism of The appearance of Oskar protein occurs coincident repression is attractive, it does not yet account for the with localization of oskar mRNA to the posterior pole roles of the RNA binding proteins other than Bru that of the Drosophila oocyte, and earlier accumulation of also act in repression. Moreover, the amount of Osk the protein is prevented by translational repression.
Journal of Biological Chemistry, 1999
Gene families normally expand by segmental genomic duplication and subsequent sequence divergence. Although copies of partially or fully processed mRNA transcripts are occasionally retrotransposed into the genome, they are usually nonfunctional ("processed pseudogenes"). The two major cytoplasmic poly(C)-binding proteins in mammalian cells, ␣CP-1 and ␣CP-2, are implicated in a spectrum of post-transcriptional controls. These proteins are highly similar in structure and are encoded by closely related mRNAs. Based on this close relationship, we were surprised to find that one of these proteins, ␣CP-2, was encoded by a multiexon gene, whereas the second gene, ␣CP-1, was identical to and colinear with its mRNA. The ␣CP-1 and ␣CP-2 genes were shown to be single copy and were mapped to separate chromosomes. The linkage groups encompassing each of the two loci were concordant between mice and humans. These data suggested that the ␣CP-1 gene was generated by retrotransposition of a fully processed ␣CP-2 mRNA and that this event occurred well before the mammalian radiation. The stringent structural conservation of ␣CP-1 and its ubiquitous tissue distribution suggested that the retrotransposed ␣CP-1 gene was rapidly recruited to a function critical to the cell and distinct from that of its ␣CP-2 progenitor.
Genes & Development, 1998
1 D epart m en t of M olecu lar G en et ics an d M icrobiology an d 2 G radu at e Program in M olecu lar Bioscien ces at U n iversit y of M edicin e an d D en t ist ry of N ew Jersey (U M D N J)/ Ru t gers U n iversit ies, Robert Wood Joh n son M edical Sch ool-U M D N J, 3 In st it u t e of Experim en t al C ardiology, C ardiology Research C en t er, M oscow , 121552 Ru ssia; 4 D epart m en t of Pediat rics, M edicin e, an d G en et ics, C en t er for M edical G en et ics, 5 Joh n s H opk in s U n iversit y Sch ool of M edicin e, H ow ard H u gh es M edical In st it u t e, Balt im ore, M arylan d 21205 U SA; an d 6 C an cer In st it u t e of N ew Jersey, Piscat aw ay, N ew Jersey 08854 U SA