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CRNKL1 is a highly selective regulator of intron-retaining HIV-1 and cellular mRNAs

Item Type:Preprint
Title:CRNKL1 is a highly selective regulator of intron-retaining HIV-1 and cellular mRNAs
Creators Name:Xiao, H. and Wyler, E. and Milek, M. and Grewe, B. and Kirchner, P. and Ekici, A. and Villela Silva, A.B.O. and Jungnickl, D. and Landthaler, M. and Ensser, A. and Überla, K.
Abstract:The HIV-1 Rev protein is a nuclear export factor for unspliced and incompletely-spliced HIV-1 RNAs. Without Rev, these intron-retaining RNAs are trapped in the nucleus. A genome-wide screen identified nine proteins of the spliceosome which all enhanced expression from the HIV-1 unspliced RNA after CRISPR/Cas knock-down. Depletion of DHX38, WDR70 and four proteins of the Prp19-associated complex (ISY1, BUD31, XAB2, CRNKL1) resulted in a more than 20-fold enhancement of unspliced HIV-1 RNA levels in the cytoplasm. Targeting of CRNKL1, DHX38, and BUD31 affected nuclear export efficiencies of the HIV-1 unspliced RNA to a much larger extent than splicing. Transcriptomic analyses further revealed that CRNKL1 also suppresses cytoplasmic levels of cellular mRNAs with selectively retained introns. Thus, CRNKL1 dependent nuclear retention seems to be a novel mechanism for the regulation of cytoplasmic levels of intron-retaining cellular mRNAs that is harnessed by HIV-1 to direct its complex splicing pattern.
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2020.02.04.934927
Date:11 February 2020
Official Publication:https://doi.org/10.1101/2020.02.04.934927
Related to:
https://edoc.mdc-berlin.de/19882/Final version

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