Mining small RNA structure elements in untranslated regions of human and mouse mRNAs using structure-based alignment

BackgroundUnTranslated Regions (UTRs) of mRNAs contain regulatory elements for various aspects of mRNA metabolism, such as mRNA localization, translation, and mRNA stability. Several RNA stem-loop structures in UTRs have been experimentally identified, including the histone 3' UTR stem-loop structure (HSL3) and iron response element (IRE). These stem-loop structures are conserved among mammalian orthologs, and exist in a group of genes encoding proteins involved in the same biological pathways. It is not known to what extent RNA structures like these exist in all mammalian UTRs.ResultsIn this paper we took a systematic approach, named GLEAN-UTR, to identify small stem-loop RNA structure elements in UTRs that are conserved between human and mouse orthologs and exist in multiple genes with common Gene Ontology terms. This approach resulted in 90 distinct RNA structure groups containing 748 structures, with HSL3 and IRE among the top hits based on conservation of structure.ConclusionOur result indicates that there may exist many conserved stem-loop structures in mammalian UTRs that are involved in coordinate post-transcriptional regulation of biological pathways.

[1]  J. Sabina,et al.  Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. , 1999, Journal of molecular biology.

[2]  J. Harney,et al.  Two distinct SECIS structures capable of directing selenocysteine incorporation in eukaryotes. , 1999, RNA.

[3]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[4]  Tala Bakheet,et al.  ARED: human AU-rich element-containing mRNA database reveals an unexpectedly diverse functional repertoire of encoded proteins , 2001, Nucleic Acids Res..

[5]  Donna R. Maglott,et al.  RefSeq and LocusLink: NCBI gene-centered resources , 2001, Nucleic Acids Res..

[6]  T. Cooper,et al.  Finding signals that regulate alternative splicing in the post-genomic era , 2002, Genome Biology.

[7]  S. Tenenbaum,et al.  Eukaryotic mRNPs may represent posttranscriptional operons. , 2002, Molecular cell.

[8]  C. Gissi,et al.  Untranslated regions of mRNAs , 2002, Genome Biology.

[9]  S. Kuersten,et al.  The power of the 3′ UTR: translational control and development , 2003, Nature Reviews Genetics.

[10]  N. Gray,et al.  Regulation of mRNA translation by 5'- and 3'-UTR-binding factors. , 2003, Trends in biochemical sciences.

[11]  Christina Gloeckner,et al.  Modern Applied Statistics With S , 2003 .

[12]  Ivo L. Hofacker,et al.  Vienna RNA secondary structure server , 2003, Nucleic Acids Res..

[13]  Graziano Pesole,et al.  PatSearch: a program for the detection of patterns and structural motifs in nucleotide sequences , 2003, Nucleic Acids Res..

[14]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[15]  Jun Hu,et al.  A method for aligning RNA secondary structures and its application to RNA motif detection , 2005, BMC Bioinformatics.

[16]  J. Wilusz,et al.  Bringing the role of mRNA decay in the control of gene expression into focus. , 2004, Trends in genetics : TIG.

[17]  William F Marzluff,et al.  Metazoan replication-dependent histone mRNAs: a distinct set of RNA polymerase II transcripts. , 2005, Current opinion in cell biology.

[18]  B. Tian,et al.  Bioinformatic identification of candidate cis-regulatory elements involved in human mRNA polyadenylation. , 2005, RNA.

[19]  F. Clark,et al.  Understanding alternative splicing: towards a cellular code , 2005, Nature Reviews Molecular Cell Biology.

[20]  P. Stadler,et al.  Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genome , 2005, Nature Biotechnology.

[21]  J. Gorodkin,et al.  Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common RNA structure. , 2006, Genome research.

[22]  Chris Sander,et al.  Prediction of human microRNA targets. , 2006, Methods in molecular biology.

[23]  Timothy R. Hughes,et al.  Considerations in the identification of functional RNA structural elements in genomic alignments , 2007, BMC Bioinformatics.

[24]  M. Turcotte,et al.  Searching for IRES. , 2006, RNA.

[25]  L. Ouafik,et al.  Identification of secondary structure in the 5′-untranslated region of the human adrenomedullin mRNA with implications for the regulation of mRNA translation , 2006, Oncogene.

[26]  T. Rouault.  The role of iron regulatory proteins in mammalian iron homeostasis and disease , 2006, Nature chemical biology.

[27]  N. Rajewsky.  microRNA target predictions in animals , 2006, Nature Genetics.

[28]  David Haussler,et al.  Identification and Classification of Conserved RNA Secondary Structures in the Human Genome , 2006, PLoS Comput. Biol..

[29]  K. Sobczak,et al.  Hairpin structure within the 3′UTR of DNA polymerase β mRNA acts as a post-transcriptional regulatory element and interacts with Hax-1 , 2007, Nucleic acids research.

[30]  W. Filipowicz,et al.  Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? , 2008, Nature Reviews Genetics.