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MBE Advance Access published online on June 2, 2009

Molecular Biology and Evolution, doi:10.1093/molbev/msp112
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© The Author 2009. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

Evolution of Vault RNAs

Peter F. Stadlera,b,c,e,d, Julian J.-L. Chenf,g, Jörg Hackermüllerc, Steve Hoffmanna, Friedemann Hornh,c, Phillip Khaitovichi, Antje K. Kretzschmarc, Axel Mosigi,b, Sonja J. Prohaskad,e,a, Xiaodong Qif, Katharina Schuttc,h and Kerstin Ullmannc,h

a Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig,Härtelstraße 16-18, D-04107 Leipzig, Germany
b Max-Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany
c Fraunhofer Institut für Zelltherapie und Immunologie (IZI), Perlickstraße 1, D-04103 Leipzig, Germany
d Department of Theoretical Chemistry, University of Vienna, Währingerstraße 17, A-1090 Wien, Austria
e Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USA
f Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA
g School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA
h Institute of Clinical Immunology and Transfusion Medicine, University Hospital Leipzig, D-04103 Leipzig, Germany
i CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, 320 Yue Yang Road, 200031 Shanghai, China

E-mail: studla{at}bioinf.uni-leipzig.de

Received for publication April 19, 2009. Accepted for publication May 14, 2009.

Vault RNAs (vtRNAs) are small, about 100nt long, polymerase III transcripts contained in the vault particles of eukaryotic cells. Presumably due to their enigmatic function, they have received little attention compared to most other non-coding RNA (ncRNA) families. Their poor sequence conservation makes homology search a complex and tedious task even within vertebrates. Here we report on a systematic and comprehensive analysis of this rapidly evolving class of ncRNAs in deuterostomes, providing a comprehensive collection of computationally predicted vtRNA genes. We find that all previously described vtRNAs are located at a conserved genomic locus linked to the protocadherin gene cluster, an association that is conserved throughout gnathostomes. Lineage specific expansions to small vtRNA gene clusters are frequently observed in this region. A second vtRNA locus is syntenically conserved across eutherian mammals. The vtRNAs at the two eutherian loci exhibit substantial differences in their promoter structures, explaining their differential expression patterns in several human cancer cell lines. In teleosts, expression of several paralogous vtRNA genes, most but not all located at the syntenically conserved protocadherin locus, was verified by RT-PCR.

Key Words: vault particle • vault RNA • micro RNA • homology search • RNA secondary structure


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