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Nucleic Acids Research 2005 33(4):1384-1398; doi:10.1093/nar/gki267
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Published online 3 March 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
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Article

Modular RNA architecture revealed by computational analysis of existing pseudoknots and ribosomal RNAs

Samuela Pasquali, Hin Hark Gan1 and Tamar Schlick1,2,*

Department of Physics, New York University 251 Mercer Street, New York, NY 10021, USA 1Department of Chemistry, New York University 251 Mercer Street, New York, NY 10021, USA 2Courant Institute of Mathematical Sciences, New York University 251 Mercer Street, New York, NY 10021, USA

*To whom correspondence should be addressed: Tel: +1 212 998 3116; Fax: +1 212 995 4152; Email: schlick{at}nyu.edu

Received December 1, 2004. Revised February 5, 2005. Accepted February 5, 2005.

Modular architecture is a hallmark of RNA structures, implying structural, and possibly functional, similarity among existing RNAs. To systematically delineate the existence of smaller topologies within larger structures, we develop and apply an efficient RNA secondary structure comparison algorithm using a newly developed two-dimensional RNA graphical representation. Our survey of similarity among 14 pseudoknots and subtopologies within ribosomal RNAs (rRNAs) uncovers eight pairs of structurally related pseudoknots with non-random sequence matches and reveals modular units in rRNAs. Significantly, three structurally related pseudoknot pairs have functional similarities not previously known: one pair involves the 3' end of brome mosaic virus genomic RNA (PKB134) and the alternative hammerhead ribozyme pseudoknot (PKB173), both of which are replicase templates for viral RNA replication; the second pair involves structural elements for translation initiation and ribosome recruitment found in the viral internal ribosome entry site (PKB223) and the V4 domain of 18S rRNA (PKB205); the third pair involves 18S rRNA (PKB205) and viral tRNA-like pseudoknot (PKB134), which probably recruits ribosomes via structural mimicry and base complementarity. Additionally, we quantify the modularity of 16S and 23S rRNAs by showing that RNA motifs can be constructed from at least 210 building blocks. Interestingly, we find that the 5S rRNA and two tree modules within 16S and 23S rRNAs have similar topologies and tertiary shapes. These modules can be applied to design novel RNA motifs via build-up-like procedures for constructing sequences and folds.


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