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DDX3 depletion represses translation of mRNAs with complex 5' UTRs

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Item Type:Article
Title:DDX3 depletion represses translation of mRNAs with complex 5' UTRs
Creators Name:Calviello, L. and Venkataramanan, S. and Rogowski, K.J. and Wyler, E. and Wilkins, K. 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. Ded1, the yeast ortholog of DDX3, is a global regulator of translation, whereas DDX3 is thought to preferentially affect 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 highly expressed mRNAs, depletion of DDX3 particularly affects the translation of a small subset of the transcriptome. We further find that DDX3 binds a site on helix 16 of the human ribosomal rRNA, placing it immediately adjacent to the mRNA entry channel. Translation changes caused by depleting DDX3 levels or expressing an inactive point mutation are different, consistent with different association of these genetic variant types with disease. Taken together, this work defines the subset of the transcriptome that is responsive to DDX3 inhibition, with relevance for basic biology and disease states where DDX3 is altered.
Keywords:5' Untranslated Regions, DEAD-box RNA Helicases, HEK293 Cells, Messenger RNA, Mutation, Protein Biosynthesis, Ribosomal RNA, Small Interfering RNA
Source:Nucleic Acids Research
ISSN:0305-1048
Publisher:Oxford University Press
Volume:49
Number:9
Page Range:5336-5350
Date:May 2021
Official Publication:https://doi.org/10.1093/nar/gkab287
PubMed:View item in PubMed

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