Genome-wide measurement of RNA secondary structure in yeast.
The structures of RNA molecules are often important for their function and regulation, yet there are no experimental techniques for genome-scale measurement of RNA structure. Here we describe a novel strategy termed parallel analysis of RNA structure (PARS), which is based on deep sequencing fragments of RNAs that were treated with structure-specific enzymes, thus providing simultaneous in vitro profiling of the secondary structure of thousands of RNA species at single nucleotide resolution. We apply PARS to profile the secondary structure of the messenger RNAs (mRNAs) of the budding yeast Saccharomyces cerevisiae and obtain structural profiles for over 3,000 distinct transcripts. Analysis of these profiles reveals several RNA structural properties of yeast transcripts, including the existence of more secondary structure over coding regions compared with untranslated regions, a three-nucleotide periodicity of secondary structure across coding regions and an anti-correlation between the efficiency with which an mRNA is translated and the structure over its translation start site. PARS is readily applicable to other organisms and to profiling RNA structure in diverse conditions, thus enabling studies of the dynamics of secondary structure at a genomic scale.
Kertesz
Michael
M
Dept. of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
Wan
Yue
Y
Howard Hughes Medical Institute, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mazor
Elad
E
Dept. of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
Rinn
John L
JL
The Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Nutter
Robert C
RC
Life Technologies, Foster City, CA 94404, USA.
Chang
Howard Y
HY
Howard Hughes Medical Institute, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Segal
Eran
E
Dept. of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.|Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
D001483:Base Sequence; D005821:Genetic Techniques; D055106:Genome-Wide Association Study; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012331:RNA, Fungal / Q000737:chemistry*; D012333:RNA, Messenger / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000235:genetics*; D014158:Transcription, Genetic
D012331:RNA, Fungal; D012333:RNA, Messenger
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