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PMID: 23150631 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Regulatory impact of RNA secondary structure across the Arabidopsis transcriptome.

The Plant cell ·Vol. 24 ·No. 11 ·2012-11-00 ·Pages 4346-59

Li F, Zheng Q, Vandivier LE, Willmann MR, Chen Y, Gregory BD

Abstract

The secondary structure of an RNA molecule plays an integral role in its maturation, regulation, and function. However, the global influence of this feature on plant gene expression is still largely unclear. Here, we use a high-throughput, sequencing-based, structure-mapping approach in conjunction with transcriptome-wide sequencing of rRNA-depleted (RNA sequencing), small RNA, and ribosome-bound RNA populations to investigate the impact of RNA secondary structure on gene expression regulation in Arabidopsis thaliana. From this analysis, we find that highly unpaired and paired RNAs are strongly correlated with euchromatic and heterochromatic epigenetic histone modifications, respectively, providing evidence that secondary structure is necessary for these RNA-mediated posttranscriptional regulatory pathways. Additionally, we uncover key structural patterns across protein-coding transcripts that indicate RNA folding demarcates regions of protein translation and likely affects microRNA-mediated regulation of mRNAs in this model plant. We further reveal that RNA folding is significantly anticorrelated with overall transcript abundance, which is often due to the increased propensity of highly structured mRNAs to be degraded and/or processed into small RNAs. Finally, we find that secondary structure affects mRNA translation, suggesting that this feature regulates plant gene expression at multiple levels. These findings provide a global assessment of RNA folding and its significant regulatory effects in a plant transcriptome.

MeSH Terms
Arabidopsis/genetics Flowers/genetics Gene Expression Regulation, Plant/genetics Gene Library Genome, Plant/genetics High-Throughput Nucleotide Sequencing MicroRNAs/genetics Models, Molecular Nucleic Acid Conformation RNA Folding RNA, Messenger/genetics RNA, Plant/genetics Sequence Analysis, RNA Transcriptome
Chemicals
MicroRNAs RNA, Messenger RNA, Plant
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Li Fan
Department of Biology, University of Pensylvania, Philadelphia, Pensylvania 19104, USA.
Zheng Qi
Vandivier Lee E
Willmann Matthew R
Chen Ying
Gregory Brian D
References (52)
52 references, click to expand
  1. Isolation of plant polysomal mRNA by differential centrifugation and ribosome immunopurification methods.
    Methods Mol Biol. 2009;553:109-26 PMID: 19588103
  2. Inhibition of polyadenylation by stable RNA secondary structure.
    Nucleic Acids Res. 1998 Apr 15;26(8):1870-6 PMID: 9518478
  3. Genome-wide association of histone H3 lysine nine methylation with CHG DNA methylation in Arabidopsis thaliana.
    PLoS One. 2008 Sep 08;3(9):e3156 PMID: 18776934
  4. Regulation of heterochromatic DNA replication by histone H3 lysine 27 methyltransferases.
    Nature. 2010 Aug 19;466(7309):987-91 PMID: 20631708
  5. The Functions of RNA-Dependent RNA Polymerases in Arabidopsis.
    Arabidopsis Book. 2011;9:e0146 PMID: 22303271
  6. Identification and characterization of multi-species conserved sequences.
    Genome Res. 2003 Dec;13(12):2507-18 PMID: 14656959
  7. Genome-wide measurement of RNA secondary structure in yeast.
    Nature. 2010 Sep 2;467(7311):103-7 PMID: 20811459
  8. Architecture and secondary structure of an entire HIV-1 RNA genome.
    Nature. 2009 Aug 6;460(7256):711-6 PMID: 19661910
  9. ChIP-seq Analysis in R (CSAR): An R package for the statistical detection of protein-bound genomic regions.
    Plant Methods. 2011 May 09;7:11 PMID: 21554688
  10. Potent effect of target structure on microRNA function.
    Nat Struct Mol Biol. 2007 Apr;14(4):287-94 PMID: 17401373
  11. Systematic discovery of structural elements governing stability of mammalian messenger RNAs.
    Nature. 2012 Apr 08;485(7397):264-8 PMID: 22495308
  12. Origins and Mechanisms of miRNAs and siRNAs.
    Cell. 2009 Feb 20;136(4):642-55 PMID: 19239886
  13. The ribosome: a molecular machine powered by RNA.
    Met Ions Life Sci. 2011;9:253-75 PMID: 22010275
  14. Perspective: machines for RNAi.
    Genes Dev. 2005 Mar 1;19(5):517-29 PMID: 15741316
  15. Origin, biogenesis, and activity of plant microRNAs.
    Cell. 2009 Feb 20;136(4):669-87 PMID: 19239888
  16. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
    Genome Biol. 2009;10(3):R25 PMID: 19261174
  17. The centrality of RNA.
    Cell. 2009 Feb 20;136(4):577-80 PMID: 19239877
  18. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
    Nat Protoc. 2009;4(1):44-57 PMID: 19131956
  19. Modulation of alternative splicing by long-range RNA structures in Drosophila.
    Nucleic Acids Res. 2009 Aug;37(14):4533-44 PMID: 19465384
  20. Variance stabilization applied to microarray data calibration and to the quantification of differential expression.
    Bioinformatics. 2002;18 Suppl 1:S96-104 PMID: 12169536
  21. RNA silencing in plants.
    Nature. 2004 Sep 16;431(7006):356-63 PMID: 15372043
  22. Role of RNA structure in regulating pre-mRNA splicing.
    Trends Biochem Sci. 2010 Mar;35(3):169-78 PMID: 19959365
  23. MicroRNAS and their regulatory roles in plants.
    Annu Rev Plant Biol. 2006;57:19-53 PMID: 16669754
  24. Regulation of translation via mRNA structure in prokaryotes and eukaryotes.
    Gene. 2005 Nov 21;361:13-37 PMID: 16213112
  25. Genome-wide double-stranded RNA sequencing reveals the functional significance of base-paired RNAs in Arabidopsis.
    PLoS Genet. 2010 Sep 30;6(9):e1001141 PMID: 20941385
  26. Computational analysis of miRNA targets in plants: current status and challenges.
    Brief Bioinform. 2011 Mar;12(2):115-21 PMID: 20858738
  27. Riboswitches: emerging themes in RNA structure and function.
    Annu Rev Biophys. 2008;37:117-33 PMID: 18573075
  28. Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution.
    Cell. 2011 Dec 23;147(7):1537-50 PMID: 22196729
  29. The role of site accessibility in microRNA target recognition.
    Nat Genet. 2007 Oct;39(10):1278-84 PMID: 17893677
  30. RNA silencing and genome regulation.
    Trends Cell Biol. 2005 May;15(5):251-8 PMID: 15866029
  31. A link between RNA metabolism and silencing affecting Arabidopsis development.
    Dev Cell. 2008 Jun;14(6):854-66 PMID: 18486559
  32. Integrative epigenomic mapping defines four main chromatin states in Arabidopsis.
    EMBO J. 2011 May 18;30(10):1928-38 PMID: 21487388
  33. Viral RNA pseudoknots: versatile motifs in gene expression and replication.
    Nat Rev Microbiol. 2007 Aug;5(8):598-610 PMID: 17632571
  34. Downstream elements of mammalian pre-mRNA polyadenylation signals: primary, secondary and higher-order structures.
    Nucleic Acids Res. 2003 Mar 1;31(5):1375-86 PMID: 12595544
  35. Vienna RNA secondary structure server.
    Nucleic Acids Res. 2003 Jul 1;31(13):3429-31 PMID: 12824340
  36. psRNATarget: a plant small RNA target analysis server.
    Nucleic Acids Res. 2011 Jul;39(Web Server issue):W155-9 PMID: 21622958
  37. RNA and disease.
    Cell. 2009 Feb 20;136(4):777-93 PMID: 19239895
  38. The dynamic landscapes of RNA architecture.
    Cell. 2009 Feb 20;136(4):604-9 PMID: 19239882
  39. Endogenous siRNA and miRNA targets identified by sequencing of the Arabidopsis degradome.
    Curr Biol. 2008 May 20;18(10):758-762 PMID: 18472421
  40. Global analysis of RNA secondary structure in two metazoans.
    Cell Rep. 2012 Jan 26;1(1):69-82 PMID: 22832108
  41. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists.
    Nucleic Acids Res. 2009 Jan;37(1):1-13 PMID: 19033363
  42. Understanding the transcriptome through RNA structure.
    Nat Rev Genet. 2011 Aug 18;12(9):641-55 PMID: 21850044
  43. Principles of microRNA-target recognition.
    PLoS Biol. 2005 Mar;3(3):e85 PMID: 15723116
  44. MicroRNAs: genomics, biogenesis, mechanism, and function.
    Cell. 2004 Jan 23;116(2):281-97 PMID: 14744438
  45. RNA-protein interactions in human health and disease.
    Semin Cell Dev Biol. 2011 Jun;22(4):359-65 PMID: 21333748
  46. Protein-RNA interactions: new genomic technologies and perspectives.
    Nat Rev Genet. 2012 Jan 18;13(2):77-83 PMID: 22251872
  47. RNA-binding proteins and post-transcriptional gene regulation.
    FEBS Lett. 2008 Jun 18;582(14):1977-86 PMID: 18342629
  48. RNA folding affects the recruitment of SR proteins by mouse and human polypurinic enhancer elements in the fibronectin EDA exon.
    Mol Cell Biol. 2004 Feb;24(3):1387-400 PMID: 14729981
  49. Ribonucleoprotein infrastructure regulating the flow of genetic information between the genome and the proteome.
    Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7018-24 PMID: 11416181
  50. A variance-stabilizing transformation for gene-expression microarray data.
    Bioinformatics. 2002;18 Suppl 1:S105-10 PMID: 12169537
  51. Selection on synonymous sites for increased accessibility around miRNA binding sites in plants.
    Mol Biol Evol. 2012 Oct;29(10):3037-44 PMID: 22490819
  52. Mechanisms of gene silencing by double-stranded RNA.
    Nature. 2004 Sep 16;431(7006):343-9 PMID: 15372041
Article Info
Journal
The Plant cell
Abbr.
Plant Cell
ISSN
1532-298X
Published
2012-11-00
Epub
2012-00-13
Pages
4346-59
Language
English
Region
England
NLM ID
9208688
PMCID
PMC3531838
Subset
IM
Grants
NIGMS NIH HHS · T32 GM007229 · United States
NHGRI NIH HHS · T32 HG000046 · United States
NIGMS NIH HHS · 5T32GM007229-37 · United States
NHGRI NIH HHS · 5T32HG000046-13 · United States
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