Home LiteratureArticle Details
PMID: 20858238 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Genome-wide analysis of mRNA decay patterns during early Drosophila development.

Genome biology ·Vol. 11 ·No. 9 ·2010-00-00 ·Pages R93

Thomsen S, Anders S, Janga SC, Huber W, Alonso CR

Abstract

The modulation of mRNA levels across tissues and time is key for the establishment and operation of the developmental programs that transform the fertilized egg into a fully formed embryo. Although the developmental mechanisms leading to differential mRNA synthesis are heavily investigated, comparatively little attention is given to the processes of mRNA degradation and how these relate to the molecular programs controlling development. Here we combine timed collection of Drosophila embryos and unfertilized eggs with genome-wide microarray technology to determine the degradation patterns of all mRNAs present during early fruit fly development. Our work studies the kinetics of mRNA decay, the contributions of maternally and zygotically encoded factors to mRNA degradation, and the ways in which mRNA decay profiles relate to gene function, mRNA localization patterns, translation rates and protein turnover. We also detect cis-regulatory sequences enriched in transcripts with common degradation patterns and propose several proteins and microRNAs as developmental regulators of mRNA decay during early fruit fly development. Finally, we experimentally validate the effects of a subset of cis-regulatory sequences and trans-regulators in vivo. Our work advances the current understanding of the processes controlling mRNA degradation during early Drosophila development, taking us one step closer to the understanding of mRNA decay processes in all animals. Our data also provide a valuable resource for further experimental and computational studies investigating the process of mRNA decay.

MeSH Terms
Animals Drosophila Proteins/metabolism Drosophila melanogaster/embryology,genetics,metabolism Embryo, Nonmammalian/embryology,metabolism Embryonic Development/genetics Gene Expression Regulation, Developmental Genome, Insect MicroRNAs/genetics,metabolism Oligonucleotide Array Sequence Analysis Ovum Polymerase Chain Reaction RNA Stability RNA, Messenger/genetics,metabolism Regulatory Sequences, Ribonucleic Acid Transcription, Genetic
Chemicals
Drosophila Proteins MicroRNAs RNA, Messenger Regulatory Sequences, Ribonucleic Acid
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Thomsen Stefan
Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. S.Thomsen@sussex.ac.uk
Anders Simon
Janga Sarath Chandra
Huber Wolfgang
Alonso Claudio R
References (114)
114 references, click to expand
  1. Primer3 on the WWW for general users and for biologist programmers.
    Methods Mol Biol. 2000;132:365-86 PMID: 10547847
  2. The three postblastoderm cell cycles of Drosophila embryogenesis are regulated in G2 by string.
    Cell. 1990 Aug 10;62(3):469-80 PMID: 2199063
  3. Microarray data quality control improves the detection of differentially expressed genes.
    Genomics. 2010 Mar;95(3):138-42 PMID: 20079422
  4. In vitro activation of Drosophila eggs.
    Dev Biol. 1983 Aug;98(2):437-45 PMID: 6409691
  5. Changes in the stability of a human H3 histone mRNA during the HeLa cell cycle.
    Mol Cell Biol. 1991 Jan;11(1):544-53 PMID: 1986245
  6. Heritable gene silencing in Drosophila using double-stranded RNA.
    Nat Biotechnol. 2000 Aug;18(8):896-8 PMID: 10932163
  7. Drosophila female sexual behavior induced by sterile males showing copulation complementation.
    Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3272-5 PMID: 10725377
  8. Nanos and pumilio establish embryonic polarity in Drosophila by promoting posterior deadenylation of hunchback mRNA.
    Development. 1997 Aug;124(15):3015-23 PMID: 9247343
  9. YA is needed for proper nuclear organization to transition between meiosis and mitosis in Drosophila.
    BMC Dev Biol. 2009 Jul 23;9:43 PMID: 19627584
  10. MicroRNA activity is suppressed in mouse oocytes.
    Curr Biol. 2010 Feb 9;20(3):265-70 PMID: 20116252
  11. Analysis of herpes simplex virus-induced mRNA destabilizing activity using an in vitro mRNA decay system.
    Nucleic Acids Res. 1991 Aug 25;19(16):4459-65 PMID: 1653415
  12. Parameter estimation for the calibration and variance stabilization of microarray data.
    Stat Appl Genet Mol Biol. 2003;2:Article3 PMID: 16646781
  13. Parameters controlling transcriptional activation during early Drosophila development.
    Cell. 1986 Mar 28;44(6):871-7 PMID: 2420468
  14. Iron-regulatory proteins, iron-responsive elements and ferritin mRNA translation.
    Int J Biochem Cell Biol. 1999 Oct;31(10):1139-52 PMID: 10582343
  15. Dynamic Hsp83 RNA localization during Drosophila oogenesis and embryogenesis.
    Mol Cell Biol. 1993 Jun;13(6):3773-81 PMID: 7684502
  16. Regulation of human histone gene expression: kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle.
    Mol Cell Biol. 1983 Apr;3(4):539-50 PMID: 6406835
  17. Coordinate initiation of Drosophila development by regulated polyadenylation of maternal messenger RNAs.
    Science. 1994 Dec 23;266(5193):1996-9 PMID: 7801127
  18. Immunofluorescence analysis of the cytoskeleton during oogenesis and early embryogenesis.
    Methods Cell Biol. 1994;44:489-505 PMID: 7707968
  19. AU-rich elements regulate Drosophila gene expression.
    Mol Cell Biol. 2009 May;29(10):2636-43 PMID: 19273595
  20. Completion of meiosis in uninseminated eggs of Drosophila melanogaster.
    Science. 1960 Sep 9;132(3428):677-8 PMID: 13817039
  21. Variance stabilization applied to microarray data calibration and to the quantification of differential expression.
    Bioinformatics. 2002;18 Suppl 1:S96-104 PMID: 12169536
  22. Drosophila maternal Hsp83 mRNA destabilization is directed by multiple SMAUG recognition elements in the open reading frame.
    Mol Cell Biol. 2008 Nov;28(22):6757-72 PMID: 18794360
  23. Regulation of maternal transcript destabilization during egg activation in Drosophila.
    Genetics. 2003 Jul;164(3):989-1001 PMID: 12871909
  24. Specific protein synthesis in cellular differentiation. III. The eggshell proteins of Drosophila melanogaster and their program of synthesis.
    Dev Biol. 1976 Mar;49(1):185-99 PMID: 815116
  25. Regulated expression of genes injected into early Drosophila embryos.
    EMBO J. 1984 Jan;3(1):165-73 PMID: 6323163
  26. Effects of RNA inhibitors on the development of Drosophila embryos permeabilized by a new technique.
    J Exp Zool. 1980 May;212(2):183-94 PMID: 6156991
  27. Drosophila Ana2 is a conserved centriole duplication factor.
    J Cell Biol. 2010 Feb 8;188(3):313-23 PMID: 20123993
  28. Microarray-based analyses of mRNA decay in the regulation of mammalian gene expression.
    Brief Funct Genomic Proteomic. 2004 Aug;3(2):112-24 PMID: 15355594
  29. A translational block to HSPG synthesis permits BMP signaling in the early Drosophila embryo.
    Development. 2008 Mar;135(6):1039-47 PMID: 18256192
  30. affy--analysis of Affymetrix GeneChip data at the probe level.
    Bioinformatics. 2004 Feb 12;20(3):307-15 PMID: 14960456
  31. Control of mRNA stability in eukaryotes.
    Biochem Soc Trans. 2006 Feb;34(Pt 1):30-4 PMID: 16246172
  32. RNAi is activated during Drosophila oocyte maturation in a manner dependent on aubergine and spindle-E.
    Genes Dev. 2002 Aug 1;16(15):1884-9 PMID: 12154120
  33. Summaries of Affymetrix GeneChip probe level data.
    Nucleic Acids Res. 2003 Feb 15;31(4):e15 PMID: 12582260
  34. Genome-wide analysis of mRNA decay in resting and activated primary human T lymphocytes.
    Nucleic Acids Res. 2002 Dec 15;30(24):5529-38 PMID: 12490721
  35. GO::TermFinder--open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes.
    Bioinformatics. 2004 Dec 12;20(18):3710-5 PMID: 15297299
  36. Mutations that perturb poly(A)-dependent maternal mRNA activation block the initiation of development.
    Development. 1996 Feb;122(2):579-88 PMID: 8625809
  37. A network of multiple regulatory layers shapes gene expression in fission yeast.
    Mol Cell. 2007 Apr 13;26(1):145-55 PMID: 17434133
  38. Smaug recruits the CCR4/POP2/NOT deadenylase complex to trigger maternal transcript localization in the early Drosophila embryo.
    Curr Biol. 2005 Feb 22;15(4):284-94 PMID: 15723788
  39. Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation.
    Science. 1988 May 13;240(4854):924-8 PMID: 2452485
  40. Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function.
    Cell. 2007 Oct 5;131(1):174-87 PMID: 17923096
  41. Changing rates of DNA and RNA synthesis in Drosophila embryos.
    Dev Biol. 1981 Feb;82(1):127-38 PMID: 6164584
  42. Developmental control of nuclear morphogenesis and anchoring by charleston, identified in a functional genomic screen of Drosophila cellularisation.
    Development. 2006 Feb;133(4):711-23 PMID: 16421189
  43. The mother-to-child transition.
    Dev Cell. 2007 Jun;12(6):847-9 PMID: 17543857
  44. Temporal reciprocity of miRNAs and their targets during the maternal-to-zygotic transition in Drosophila.
    Curr Biol. 2008 Apr 8;18(7):501-6 PMID: 18394895
  45. Transcript stability in the protein interaction network of Escherichia coli.
    Mol Biosyst. 2009 Feb;5(2):154-62 PMID: 19156261
  46. The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism.
    Curr Biol. 2003 Apr 29;13(9):790-5 PMID: 12725740
  47. Global analyses of mRNA translational control during early Drosophila embryogenesis.
    Genome Biol. 2007;8(4):R63 PMID: 17448252
  48. Genome-wide analysis of mRNA stability using transcription inhibitors and microarrays reveals posttranscriptional control of ribosome biogenesis factors.
    Mol Cell Biol. 2004 Jun;24(12):5534-47 PMID: 15169913
  49. Spatial and temporal control of RNA stability.
    Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7025-8 PMID: 11416182
  50. Simpleaffy: a BioConductor package for Affymetrix Quality Control and data analysis.
    Bioinformatics. 2005 Sep 15;21(18):3683-5 PMID: 16076888
  51. Drosophila RNA binding proteins.
    Int Rev Cytol. 2006;248:43-139 PMID: 16487790
  52. miRBase: tools for microRNA genomics.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D154-8 PMID: 17991681
  53. A gradient of bicoid protein in Drosophila embryos.
    Cell. 1988 Jul 1;54(1):83-93 PMID: 3383244
  54. Global analysis of mRNA decay and abundance in Escherichia coli at single-gene resolution using two-color fluorescent DNA microarrays.
    Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9697-702 PMID: 12119387
  55. Mechanisms of RNA localization and translational regulation.
    Curr Opin Genet Dev. 2000 Oct;10(5):476-88 PMID: 10980424
  56. Conservation of the protein composition and electron microscopy structure of Drosophila melanogaster and human spliceosomal complexes.
    Mol Cell Biol. 2009 Jan;29(1):281-301 PMID: 18981222
  57. Bicaudal-C recruits CCR4-NOT deadenylase to target mRNAs and regulates oogenesis, cytoskeletal organization, and its own expression.
    Dev Cell. 2007 Nov;13(5):691-704 PMID: 17981137
  58. Regulation of messenger RNA stability in mouse erythroleukemia cells.
    J Mol Biol. 1985 Jan 20;181(2):231-9 PMID: 3856689
  59. arrayQualityMetrics--a bioconductor package for quality assessment of microarray data.
    Bioinformatics. 2009 Feb 1;25(3):415-6 PMID: 19106121
  60. Transitioning from egg to embryo: triggers and mechanisms of egg activation.
    Dev Dyn. 2008 Mar;237(3):527-44 PMID: 18265018
  61. Regulation and function of maternal mRNA destabilization during early Drosophila development.
    Differentiation. 2007 Jul;75(6):482-506 PMID: 17509066
  62. Ovulation triggers activation of Drosophila oocytes.
    Dev Biol. 2001 Jun 15;234(2):416-24 PMID: 11397010
  63. Control of messenger RNA stability in higher eukaryotes.
    Trends Genet. 1996 May;12(5):171-5 PMID: 8984731
  64. In vivo stable isotope labeling of fruit flies reveals post-transcriptional regulation in the maternal-to-zygotic transition.
    Mol Cell Proteomics. 2009 Jul;8(7):1566-78 PMID: 19321433
  65. mRNA stability in mammalian cells.
    Microbiol Rev. 1995 Sep;59(3):423-50 PMID: 7565413
  66. Localized Bicaudal-C RNA encodes a protein containing a KH domain, the RNA binding motif of FMR1.
    EMBO J. 1995 May 1;14(9):2043-55 PMID: 7538070
  67. Genome-wide analysis of mRNAs regulated by the THO complex in Drosophila melanogaster.
    Nat Struct Mol Biol. 2004 Jun;11(6):558-66 PMID: 15133499
  68. Decay rates of human mRNAs: correlation with functional characteristics and sequence attributes.
    Genome Res. 2003 Aug;13(8):1863-72 PMID: 12902380
  69. Permeabilization of Drosophila eggs.
    Dev Biol. 1973 Dec;35(2):382-7 PMID: 4207363
  70. Global RNA half-life analysis in Escherichia coli reveals positional patterns of transcript degradation.
    Genome Res. 2003 Feb;13(2):216-23 PMID: 12566399
  71. Gene expression during the life cycle of Drosophila melanogaster.
    Science. 2002 Sep 27;297(5590):2270-5 PMID: 12351791
  72. Ypsilon Schachtel, a Drosophila Y-box protein, acts antagonistically to Orb in the oskar mRNA localization and translation pathway.
    Development. 2002 Jan;129(1):197-209 PMID: 11782413
  73. The Drosophila calcipressin sarah is required for several aspects of egg activation.
    Curr Biol. 2006 Jul 25;16(14):1441-6 PMID: 16860744
  74. Mass isolation of fly tissues.
    Methods Cell Biol. 1994;44:129-42 PMID: 7707947
  75. Bioconductor: open software development for computational biology and bioinformatics.
    Genome Biol. 2004;5(10):R80 PMID: 15461798
  76. Evidence that processed small dsRNAs may mediate sequence-specific mRNA degradation during RNAi in Drosophila embryos.
    Curr Biol. 2000 Oct 5;10(19):1191-200 PMID: 11050387
  77. Iterative Group Analysis (iGA): a simple tool to enhance sensitivity and facilitate interpretation of microarray experiments.
    BMC Bioinformatics. 2004 Mar 29;5:34 PMID: 15050037
  78. Rates of synthesis of major classes of RNA in Drosophila embryos.
    Dev Biol. 1979 May;70(1):217-31 PMID: 110635
  79. Evolution, biogenesis, expression, and target predictions of a substantially expanded set of Drosophila microRNAs.
    Genome Res. 2007 Dec;17(12):1850-64 PMID: 17989254
  80. Activation of the meiotic divisions in Drosophila oocytes.
    Dev Biol. 1997 Mar 15;183(2):195-207 PMID: 9126294
  81. The Drosophila pumilio gene encodes two functional protein isoforms that play multiple roles in germline development, gonadogenesis, oogenesis and embryogenesis.
    Genetics. 1999 Sep;153(1):235-50 PMID: 10471709
  82. Changing rates of histone mRNA synthesis and turnover in Drosophila embryos.
    Cell. 1980 Oct;21(3):717-27 PMID: 6777046
  83. Immunoglobulin mRNA stability varies during B lymphocyte differentiation.
    EMBO J. 1988 Apr;7(4):1041-6 PMID: 3136013
  84. SMAUG is a major regulator of maternal mRNA destabilization in Drosophila and its translation is activated by the PAN GU kinase.
    Dev Cell. 2007 Jan;12(1):143-55 PMID: 17199047
  85. Dissecting the expression dynamics of RNA-binding proteins in posttranscriptional regulatory networks.
    Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20300-5 PMID: 19918083
  86. Identification of tightly regulated groups of genes during Drosophila melanogaster embryogenesis.
    Mol Syst Biol. 2007;3:72 PMID: 17224916
  87. Zygotic degradation of two maternal Cdc25 mRNAs terminates Drosophila's early cell cycle program.
    Genes Dev. 1996 Aug 1;10(15):1966-77 PMID: 8756353
  88. Cell cycle control by the nucleo-cytoplasmic ratio in early Drosophila development.
    Cell. 1986 Jan 31;44(2):365-72 PMID: 3080248
  89. Unmasking activation of the zygotic genome using chromosomal deletions in the Drosophila embryo.
    PLoS Biol. 2007 May;5(5):e117 PMID: 17456005
  90. Autoradiographic study of protein and RNA formation during early development of Drosophila eggs.
    Dev Biol. 1976 Apr;49(2):425-37 PMID: 817947
  91. Bicaudal C and trailer hitch have similar roles in gurken mRNA localization and cytoskeletal organization.
    Dev Biol. 2009 Apr 15;328(2):434-44 PMID: 19217894
  92. Genome-wide identification of mRNAs associated with the translational regulator PUMILIO in Drosophila melanogaster.
    Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4487-92 PMID: 16537387
  93. Detecting microRNA binding and siRNA off-target effects from expression data.
    Nat Methods. 2008 Dec;5(12):1023-5 PMID: 18978784
  94. Nonsense-mediated mRNA decay in Drosophila: at the intersection of the yeast and mammalian pathways.
    EMBO J. 2003 Aug 1;22(15):3960-70 PMID: 12881430
  95. The maternal-to-zygotic transition: a play in two acts.
    Development. 2009 Sep;136(18):3033-42 PMID: 19700615
  96. Measuring mRNA stability during early Drosophila embryogenesis.
    Methods Enzymol. 2008;448:299-334 PMID: 19111183
  97. smaug protein represses translation of unlocalized nanos mRNA in the Drosophila embryo.
    Genes Dev. 1996 Oct 15;10(20):2600-9 PMID: 8895661
  98. Precision and functional specificity in mRNA decay.
    Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5860-5 PMID: 11972065
  99. Joint action of two RNA degradation pathways controls the timing of maternal transcript elimination at the midblastula transition in Drosophila melanogaster.
    EMBO J. 1999 May 4;18(9):2610-20 PMID: 10228172
  100. MicroRNA function is globally suppressed in mouse oocytes and early embryos.
    Curr Biol. 2010 Feb 9;20(3):271-7 PMID: 20116247
  101. East of EDEN was a poly(A) tail.
    Biol Cell. 2003 May-Jun;95(3-4):211-9 PMID: 12867084
  102. Mass fractionation of Drosophila egg chambers.
    Dev Biol. 1977 Jun;57(2):385-92 PMID: 194805
  103. Developmental regulation of bicoid mRNA stability is mediated by the first 43 nucleotides of the 3' untranslated region.
    Mol Cell Biol. 1998 May;18(5):2892-900 PMID: 9566908
  104. tudor, a gene required for assembly of the germ plasm in Drosophila melanogaster.
    Cell. 1985 Nov;43(1):97-104 PMID: 3935320
  105. Genomic-scale measurement of mRNA turnover and the mechanisms of action of the anti-cancer drug flavopiridol.
    Genome Biol. 2001;2(10):RESEARCH0041 PMID: 11597333
  106. Mitotic domains reveal early commitment of cells in Drosophila embryos.
    Development. 1989 Sep;107(1):1-22 PMID: 2516798
  107. Genome-wide analysis of mRNAs regulated by the nonsense-mediated and 5' to 3' mRNA decay pathways in yeast.
    Mol Cell. 2003 Dec;12(6):1439-52 PMID: 14690598
  108. Nonsense-mediated messenger RNA decay is initiated by endonucleolytic cleavage in Drosophila.
    Nature. 2004 Jun 3;429(6991):575-8 PMID: 15175755
  109. Isolation of a ribonucleoprotein complex involved in mRNA localization in Drosophila oocytes.
    J Cell Biol. 2000 Feb 7;148(3):427-40 PMID: 10662770
  110. Genome-wide analysis of mRNA decay rates and their determinants in Arabidopsis thaliana.
    Plant Cell. 2007 Nov;19(11):3418-36 PMID: 18024567
  111. Setting the stage for development: mRNA translation and stability during oocyte maturation and egg activation in Drosophila.
    Dev Dyn. 2005 Mar;232(3):593-608 PMID: 15704150
  112. An essential role for the RNA-binding protein Smaug during the Drosophila maternal-to-zygotic transition.
    Development. 2009 Mar;136(6):923-32 PMID: 19234062
  113. The molecular chaperone Hsp90 is a component of the cap-binding complex and interacts with the translational repressor Cup during Drosophila oogenesis.
    Gene. 2009 Mar 1;432(1-2):67-74 PMID: 19101615
  114. Effect of DNA inhibitors upon DNA synthesis and development of Drosophila embryos.
    J Exp Zool. 1980 May;212(2):195-204 PMID: 6772737
Article Info
Journal
Genome biology
Abbr.
Genome Biol
ISSN
1474-760X
Published
2010-00-00
Epub
2010-00-21
Pages
R93
Language
English
Region
England
NLM ID
100960660
PMCID
PMC2965385
Subset
IM
Grants
Biotechnology and Biological Sciences Research Council · United Kingdom
Medical Research Council · United Kingdom
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com