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Molecular and Cellular Biology, May 2008, p. 3008-3019, Vol. 28, No. 9
0270-7306/08/$08.00+0     doi:10.1128/MCB.01800-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Translational Control by a Small RNA: Dendritic BC1 RNA Targets the Eukaryotic Initiation Factor 4A Helicase Mechanism{triangledown} ,{dagger}

Daisy Lin,1,2 Tatyana V. Pestova,2,3 Christopher U. T. Hellen,2,3 and Henri Tiedge1,2,4*

The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology,1 Program in Molecular and Cellular Biology,2 Department of Microbiology and Immunology,3 Department of Neurology, State University of New York, Health Science Center at Brooklyn, Brooklyn, New York 112034

Received 2 October 2007/ Returned for modification 7 November 2007/ Accepted 21 February 2008

Translational repressors, increasing evidence suggests, participate in the regulation of protein synthesis at the synapse, thus providing a basis for the long-term plastic modulation of synaptic strength. Dendritic BC1 RNA is a non-protein-coding RNA that represses translation at the level of initiation. However, the molecular mechanism of BC1 repression has remained unknown. Here we identify the catalytic activity of eukaryotic initiation factor 4A (eIF4A), an ATP-dependent RNA helicase, as a target of BC1-mediated translational control. BC1 RNA specifically blocks the RNA duplex unwinding activity of eIF4A but, at the same time, stimulates its ATPase activity. BC200 RNA, the primate-specific BC1 counterpart, targets eIF4A activity in identical fashion, as a result decoupling ATP hydrolysis from RNA duplex unwinding. In vivo, BC1 RNA represses translation of a reporter mRNA with 5' secondary structure. The eIF4A mechanism places BC RNAs in a central position to modulate protein synthesis in neurons.

* Corresponding author. Mailing address: The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, State University of New York, Health Science Center at Brooklyn, 450 Clarkson Avenue, Brooklyn, NY 11203. Phone: (718) 270-1370. Fax: (718) 270-2241. E-mail: htiedge{at}downstate.edu

{triangledown} Published ahead of print on 3 March 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, May 2008, p. 3008-3019, Vol. 28, No. 9
0270-7306/08/$08.00+0     doi:10.1128/MCB.01800-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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