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DDX3 depletion selectively represses translation of structured mRNAs

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Item Type:Preprint
Title:DDX3 depletion selectively represses translation of structured mRNAs
Creators Name:Calviello, L. and Venkataramanan, S. and Rogowski, K.J. and Wyler, E. and Tejura, M. and Thai, B. and Krol, J. and Filipowicz, W. and Landthaler, M. and Floor, S.N.
Abstract:DDX3 is an RNA chaperone of the DEAD-box family that regulates translation. Its yeast ortholog Ded1 controls the translation of nearly all mRNAs, whereas DDX3 is thought to regulate only a subset of mRNAs. However, the set of mRNAs that are regulated by DDX3 are unknown, along with the relationship between DDX3 binding and activity. Here, we use ribosome profiling, RNA-seq, and PAR-CLIP to define the set of mRNAs that are regulated by DDX3 in human cells. We find that while DDX3 binds most expressed mRNAs, depletion of DDX3 affects the translation level of only a small subset of the transcriptome. We further find that DDX3 binds a site on helix 16 of the human ribosome, placing it immediately adjacent to the mRNA entry channel and translation factor eIF4B. Translation changes caused by depleting DDX3 levels or through chemical inhibition mimicking a dominant negative allele are different. Taken together, our data defines the subset of the transcriptome that is responsive to DDX3 inhibition, with relevance for basic biology and disease states where DDX3 expression is altered.
Keywords:Translational Control, DEAD-Box Proteins, RNA, PAR-CLIP, Ribosome Profiling, Post-Transcriptional Control
Source:bioRxiv
Publisher:Cold Spring Harbor Laboratory Press (U.S.A.)
Article Number:589218
Date:26 March 2019
Official Publication:https://doi.org/10.1101/589218

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