Determinants of <i>Drosophila fushi tarazu</i> mRNA Instability

Riedl, Ann; Jacobs-­Lorena, Marcelo

doi:10.1128/mcb.16.6.3047

Cited by 14 publications

(25 citation statements)

References 46 publications

(49 reference statements)

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“…For example, the R-H-R transcript could be unstable due to loss of such elements. rpA1 has been used previously as a backbone with which to map instability elements within the bicoid and fushi tarazu mRNAs (17,19,26,34). Since the bicoid and fushi tarazu instability elements function in the presence of the rpA1 5Ј UTR and/or ORF, we favor-and subsequent experiments presented below support-the interpretation that the Hsp83 mRNA contains instability elements.…”

Section: Resultssupporting

confidence: 54%

Drosophila Maternal Hsp83 mRNA Destabilization Is Directed by Multiple SMAUG Recognition Elements in the Open Reading Frame

Semotok

Luo

Cooperstock

et al. 2008

Molecular and Cellular Biology

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SMAUG (SMG) is an RNA-binding protein that functions as a key component of a transcript degradationpathway that eliminates maternal mRNAs in the bulk cytoplasm of activated Drosophila melanogaster eggs. We previously showed that SMG destabilizes maternal Hsp83 mRNA by recruiting the CCR4-NOT deadenylase to trigger decay; however, the cis-acting elements through which this was accomplished were unknown. Here we show that Hsp83 transcript degradation is regulated by a major element, the Hsp83 mRNA instability element (HIE), which maps to a 615-nucleotide region of the open reading frame (ORF). The HIE is sufficient for association of a transgenic mRNA with SMG protein as well as for SMG-dependent destabilization. Although the Hsp83 mRNA is translated in the early embryo, we show that translation of the mRNA is not necessary for destabilization; indeed, the HIE functions even when located in an mRNA's 3 untranslated region. The Hsp83 mRNA contains eight predicted SMG recognition elements (SREs); all map to the ORF, and six reside within the HIE. Mutation of a single amino acid residue that is essential for SMG's interaction with SREs stabilizes endogenous Hsp83 transcripts. Furthermore, simultaneous mutation of all eight predicted SREs also results in transcript stabilization. A plausible model is that the multiple, widely distributed SREs in the ORF enable some SMG molecules to remain bound to the mRNA despite ribosome transit through any individual SRE. Thus, SMG can recruit the CCR4-NOT deadenylase to trigger Hsp83 mRNA degradation despite the fact that it is being translated.

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Section: Resultssupporting

confidence: 54%

Drosophila Maternal Hsp83 mRNA Destabilization Is Directed by Multiple SMAUG Recognition Elements in the Open Reading Frame

Semotok

Luo

Cooperstock

et al. 2008

Molecular and Cellular Biology

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“…In the 3Ј UTR there are four dispersed ATTTA motifs, which are found in a number of cytokines, lymphokines, and proto-oncogenes (Shaw and Kamen 1986). In addition, a A/TTTGTA motif that was identified in the pair-rule gene ftz (Riedl and Jacobs-Lorena 1996) is present in two copies in the 3Ј UTR and one copy in the 5Ј UTR of upd. These elements could contribute to the rapidly changing pattern of upd mRNA accumulation found in the early embryo.…”

Section: Yc43mentioning

confidence: 99%

Drosophila unpaired encodes a secreted protein that activates the JAK signaling pathway

Harrison¹,

McCoon²,

Binari³

et al. 1998

Genes Dev.

334

337

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In vertebrates, many cytokines and growth factors have been identified as activators of the JAK/STAT signaling pathway. In Drosophila, JAK and STAT molecules have been isolated, but no ligands or receptors capable of activating the pathway have been described. We have characterized the unpaired (upd) gene, which displays the same distinctive embryonic mutant defects as mutations in the Drosophila JAK (hopscotch) and STAT (stat92E) genes. Upd is a secreted protein, associated with the extracellular matrix, that activates the JAK pathway. We propose that Upd is a ligand that relies on JAK signaling to stimulate transcription of pair-rule genes in a segmentally restricted manner in the early Drosophila embryo.

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“…These hybrid genes were reported previously (12). Briefly, the 7.9-kb KpnI-SalI fragment (Ff5) and the 4.0-kb SalI-KpnI fragment (f3) were obtained from the ftz genomic clone A439 (13).…”

Section: Ff5r3 and Rr5f3 (See Fig 1a)mentioning

confidence: 99%

“…In turn, this f3ϩaldB fragment was fused to Ff5 to produce FftzϩaldB. A f3-FIE3 fragment that lacks the 201-base pair FIE3 sequence was obtained as previously described (12). FftzϩaldB-FIE3 was constructed as described for FftzϩaldB, except that f3-FIE3 was used instead of f3.…”

Section: Ff5r3 and Rr5f3 (See Fig 1a)mentioning

confidence: 99%

“…Earlier studies from this laboratory using hybrid genes that fuse ftz sequences to the stable ribosomal protein A1 (rpA1) mRNA provided evidence for at least two destabilizing elements in ftz mRNA (12). One consisted of a 201-nucleotide element, including an essential 68-nucleotide sequence, located in the 3Ј UTR 1 and termed FIE3 (ftz instability element 3Ј).…”

mentioning

confidence: 99%

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Functional Mapping of Destabilizing Elements in the Protein-coding Region of the Drosophila fushi tarazumRNA

Ito

Jacobs-Lorena

2001

Journal of Biological Chemistry

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The instability of the fushi tarazu (ftz) mRNA is essential for the proper development of the Drosophila embryo. Previously, we identified a 201-nucleotide instability element (FIE3) in the 3 untranslated region (UTR) of the ftz mRNA. Here we report on the identification of two additional elements in the protein-coding region of the message: the 63-nucleotide-long FIE5-1 and the 69-nucleotide-long FIE5-2. The function of both elements was position-dependent; the same elements destabilized RNAs when present within the coding region but did not when embedded in the 3 UTR of the hybrid mRNAs. We conclude that ftz mRNA has three redundant instability elements, two in the protein-coding region and one in the 3 UTR. Although each instability element is sufficient to destabilize a heterologous mRNA, the destabilizing activity of the two 5-elements depended on their position within the message.Drosophila embryonic development depends on the precise temporal and spatial expression of maternal and zygotic pattern-forming genes (1). Maternal pattern-forming genes are transcribed during oogenesis, and their mRNA abundance decreases rapidly in the early embryo. Moreover, many mRNAs encoded by zygotic pattern-forming genes undergo dramatic changes in abundance and spatial distribution during early embryogenesis. To achieve these rapid changes, especially for rapid down-regulation, transcriptional control alone is insufficient, and regulation at the level of mRNA stability is essential. For instance, the maternal bicoid mRNA is completely stable during the first 2 h of embryogenesis but is rapidly destabilized at cellularization of the blastoderm (2). As discussed in the following text, the zygotic fushi tarazu (ftz) mRNA is one of the most unstable eukaryotic mRNAs known. Given that most mRNAs in the Drosophila embryo are constitutively stable (30), the question arises how selected mRNAs in the same embryo cytoplasm are targeted for degradation. Recognition of the targeted RNAs by the RNA degrading machinery must involve cis-acting sequences. These sequences are the focus of the present study.ftz is a member of the pair-rule class of segmentation genes and one of the best characterized early zygotic genes. In early embryos ftz mRNA is detected only from about 1.5 to 4.5 h after fertilization. When first expressed, ftz mRNA is uniformly distributed through the embryo (4). As development progresses, its distribution first becomes restricted to a region comprising from 15 to 65% of egg length, then to four broad bands, and finally to seven narrow stripes that encircle the embryo (4 -6). The seven stripes are short-lived, and no ftz mRNA is detected by 5 h after fertilization. This rapid change of expression pattern and formation of stripes in a short time span can be attributed to the termination of transcription in interstripe regions coupled with rapid mRNA turnover. The need for rapid mRNA turnover is emphasized by the fact that the FTZ protein activates its own transcription in a positive feedback loop (7). Thus, it is impor...

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Determinants of Drosophila fushi tarazu mRNA Instability

Cited by 14 publications

References 46 publications

Drosophila Maternal Hsp83 mRNA Destabilization Is Directed by Multiple SMAUG Recognition Elements in the Open Reading Frame

Drosophila Maternal Hsp83 mRNA Destabilization Is Directed by Multiple SMAUG Recognition Elements in the Open Reading Frame

Drosophila unpaired encodes a secreted protein that activates the JAK signaling pathway

Functional Mapping of Destabilizing Elements in the Protein-coding Region of the Drosophila fushi tarazumRNA

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