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Science 309 (5740): 1570-1573

Copyright © 2005 by the American Association for the Advancement of Science

A Strategy for Probing the Function of Noncoding RNAs Finds a Repressor of NFAT

A. T. Willingham,1 A. P. Orth,2 S. Batalov,2 E. C. Peters,2 B. G. Wen,2 P. Aza-Blanc,2 J. B. Hogenesch,2*{dagger} P. G. Schultz1,2{dagger}

Abstract: Noncoding RNA molecules (ncRNAs) have been implicated in numerous biological processes including transcriptional regulation and the modulation of protein function. Yet, in spite of the apparent abundance of ncRNA, little is known about the biological role of the projected thousands of ncRNA genes present in the human genome. To facilitate functional analysis of these RNAs, we have created an arrayed library of short hairpin RNAs (shRNAs) directed against 512 evolutionarily conserved putative ncRNAs and, via cell-based assays, we have begun to determine their roles in cellular pathways. Using this system, we have identified an ncRNA repressor of the nuclear factor of activated T cells (NFAT), which interacts with multiple proteins including members of the importin-beta superfamily and likely functions as a specific regulator of NFAT nuclear trafficking.

1 Department of Chemistry, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.

* Present address: Scripps Florida, 5353 Parkside Drive—RF1, Jupiter, FL 33458, USA.

{dagger} To whom correspondence should be addressed. E-mail: hogenesch{at}scripps.edu (J.B.H.); schultz{at}scripps.edu (P.G.S.)

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