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A ubiquitous GC content signature underlies multimodal post-transcriptional regulation by DDX3X

ABSTRACT: The road from transcription to protein synthesis is paved with many obstacles, allowing for several modes of post-transcriptional regulation of gene expression. A fundamental player in mRNA biology, DDX3X is an RNA binding protein that regulates mRNA translation. By monitoring dynamics of mRNA abundance and translation following DDX3X depletion, we observe stabilization of translationally suppressed mRNA. We used interpretable statistical learning models to uncover GC content in the coding sequence as the major feature underlying RNA stabilization. GC content-related mRNA regulation is detectable in other studies, including hundreds of ENCODE datasets and recent work focusing on mRNA dynamics in the cell cycle. We provide further evidence for mRNA stabilization by detailed analysis of RNA-seq profiles in hundreds of samples, including a recently published Ddx3x conditional mouse model exhibiting cell cycle and neurogenesis defects. Our study identifies a ubiquitous feature underlying mRNA regulation and highlights the importance of quantifying multiple steps of the gene expression cascade, where RNA abundance and protein production are often uncoupled.

ORGANISM(S): Homo sapiens

PROVIDER: GSE218433 | GEO | 2023/08/08

REPOSITORIES: GEO

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