Genome-wide Measurement of RNA Secondary Structure in Yeast
Michael Kertesz1*, Yue Wan2*, Elad
Mazor1, John L. Rinn3, Robert
C. Nutter4, Howard Y. Chang2†, Eran
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 mRNAs of the budding yeast
S. cerevisiae and obtain structural profiles for over 3000 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 to
untranslated regions, a three-nucleotide periodicity of secondary
structure across coding regions, and a relationship between the
efficiency with which an mRNA is translated and the lack of
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.
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1 Dept. of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
2 Howard Hughes Medical Institute, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
3 The Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA
4 Life Technologies, Foster City, CA 94404, USA
5 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
* These authors contributed equally to this work.
† Correspondence should be addressed to H.C. or E.S. .