Translational control by a small RNA: dendritic BC1 RNA targets the eukaryotic initiation factor 4A helicase mechanism.
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.
Lin
Daisy
D
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, USA. htiedge@downstate.edu
Pestova
Tatyana V
TV
Hellen
Christopher U T
CU
Tiedge
Henri
H
D024506:5' Flanking Region; D002460:Cell Line; D003712:Dendrites / Q000378:metabolism*; D039601:Eukaryotic Initiation Factor-4A / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D020733:RNA, Small Cytoplasmic / Q000502:physiology*; D022661:RNA, Untranslated / Q000502:physiology
C117734:BC1 RNA; D020733:RNA, Small Cytoplasmic; D022661:RNA, Untranslated; D039601:Eukaryotic Initiation Factor-4A