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  • 1
    Publication Date: 2014-03-22
    Description: Nonsense-mediated messenger RNA (mRNA) decay (NMD) is a mRNA degradation pathway that regulates a significant portion of the transcriptome. The expression levels of numerous genes are known to be altered in NMD mutants, but it is not known which of these transcripts is a direct pathway target. Here, we present the first genome-wide analysis of direct NMD targeting in an intact animal. By using rapid reactivation of the NMD pathway in a Drosophila melanogaster NMD mutant and globally monitoring of changes in mRNA expression levels, we can distinguish between primary and secondary effects of NMD on gene expression. Using this procedure, we identified 168 candidate direct NMD targets in vivo . Remarkably, we found that 81% of direct target genes do not show increased expression levels in an NMD mutant, presumably due to feedback regulation. Because most previous studies have used up-regulation of mRNA expression as the only means to identify NMD-regulated transcripts, our results provide new directions for understanding the roles of the NMD pathway in endogenous gene regulation during animal development and physiology. For instance, we show clearly that direct target genes have longer 3' untranslated regions compared with nontargets, suggesting long 3' untranslated regions target mRNAs for NMD in vivo . In addition, we investigated the role of NMD in suppressing transcriptional noise and found that although the transposable element Copia is up-regulated in NMD mutants, this effect appears to be indirect.
    Electronic ISSN: 2160-1836
    Topics: Biology
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  • 2
    Publication Date: 2008-10-22
    Description: In all animals, the initial events of embryogenesis are controlled by maternal gene products that are deposited into the developing oocyte. At some point after fertilization, control of embryogenesis is transferred to the zygotic genome in a process called the maternal-to-zygotic transition. During this time, many maternal RNAs are degraded and transcription of zygotic RNAs ensues. There is a long-standing question as to which factors regulate these events. The recent findings that microRNAs and Smaug mediate maternal transcript degradation have shed new light on this aspect of the problem. However, the transcription factor(s) that activate the zygotic genome remain elusive. The discovery that many of the early transcribed genes in Drosophila share a cis-regulatory heptamer motif, CAGGTAG and related sequences, collectively referred to as TAGteam sites raised the possibility that a dedicated transcription factor could interact with these sites to activate transcription. Here we report that the zinc-finger protein Zelda (Zld; Zinc-finger early Drosophila activator) binds specifically to these sites and is capable of activating transcription in transient transfection assays. Mutant embryos lacking zld are defective in cellular blastoderm formation, and fail to activate many genes essential for cellularization, sex determination and pattern formation. Global expression profiling confirmed that Zld has an important role in the activation of the early zygotic genome and suggests that Zld may also regulate maternal RNA degradation during the maternal-to-zygotic transition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597674/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597674/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liang, Hsiao-Lan -- Nien, Chung-Yi -- Liu, Hsiao-Yun -- Metzstein, Mark M -- Kirov, Nikolai -- Rushlow, Christine -- GM63024/GM/NIGMS NIH HHS/ -- R01 GM063024/GM/NIGMS NIH HHS/ -- R01 GM063024-01A1/GM/NIGMS NIH HHS/ -- R01 GM063024-02/GM/NIGMS NIH HHS/ -- R01 GM063024-03/GM/NIGMS NIH HHS/ -- R01 GM063024-04/GM/NIGMS NIH HHS/ -- R01 GM063024-05/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Nov 20;456(7220):400-3. doi: 10.1038/nature07388. Epub 2008 Oct 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, New York University, 100 Washington Square East, New York, New York 10003, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18931655" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastoderm/cytology/embryology/metabolism ; Body Patterning/genetics ; Drosophila Proteins/deficiency/genetics/*metabolism ; Drosophila melanogaster/cytology/*embryology/*genetics ; Female ; Gene Deletion ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Genome, Insect/*genetics ; Male ; RNA Stability ; RNA, Messenger, Stored/genetics/metabolism ; Sex Determination Processes ; Transcription Factors/deficiency/genetics/*metabolism ; Transcriptional Activation ; *Zinc Fingers ; Zygote/cytology/growth & development/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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