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A ubiquitous GC content signature underlies multimodal mRNA regulation by DDX3X.

التفاصيل البيبلوغرافية
العنوان: A ubiquitous GC content signature underlies multimodal mRNA regulation by DDX3X.
المؤلفون: Jowhar Z; Department of Cell and Tissue Biology, UCSF, San Francisco, USA.; Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA, 94158, USA.; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, 94158, USA., Xu A; Department of Cell and Tissue Biology, UCSF, San Francisco, USA.; Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA, 94158, USA.; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, 94158, USA., Venkataramanan S; Department of Cell and Tissue Biology, UCSF, San Francisco, USA., Dossena F; Human Technopole, Milan, Italy., Hoye ML; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, USA., Silver DL; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, USA.; Department of Cell Biology, Duke University Medical Center, Durham, USA.; Duke Regeneration Center, Duke University Medical Center, Durham, USA.; Department of Neurobiology, Duke University Medical Center, Durham, USA.; Duke Institute for Brain Sciences, Duke University Medical Center, Durham, USA., Floor SN; Department of Cell and Tissue Biology, UCSF, San Francisco, USA. Stephen.Floor@ucsf.edu.; Helen Diller Family Comprehensive Cancer Center, San Francisco, USA. Stephen.Floor@ucsf.edu., Calviello L; Human Technopole, Milan, Italy. Lorenzo.Calviello@fht.org.
المصدر: Molecular systems biology [Mol Syst Biol] 2024 Mar; Vol. 20 (3), pp. 276-290. Date of Electronic Publication: 2024 Jan 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: EMBO Press Country of Publication: England NLM ID: 101235389 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1744-4292 (Electronic) Linking ISSN: 17444292 NLM ISO Abbreviation: Mol Syst Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2024- : Heidelberg : EMBO Press
Original Publication: London : Nature Pub. Group, c2005-
مواضيع طبية MeSH: Gene Expression Regulation* , RNA*, Animals ; Mice ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Base Composition ; Cell Cycle/genetics
مستخلص: 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 is DDX3X, an RNA binding protein that canonically regulates mRNA translation. By monitoring dynamics of mRNA abundance and translation following DDX3X depletion, we observe stabilization of translationally suppressed mRNAs. We use interpretable statistical learning models to uncover GC content in the coding sequence as the major feature underlying RNA stabilization. This result corroborates GC content-related mRNA regulation 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 Ddx3x conditional knockout 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.
(© 2024. The Author(s).)
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معلومات مُعتمدة: DP2 GM132932 United States GM NIGMS NIH HHS; T32 GM007618 United States GM NIGMS NIH HHS; R01 NS120667 United States NS NINDS NIH HHS; S10 OD028511 United States OD NIH HHS; F30 HD110250 United States HD NICHD NIH HHS
فهرسة مساهمة: Keywords: Computational Biology; DDX3X; Transcriptomics; Translation; mRNA Biology
المشرفين على المادة: 0 (RNA, Messenger)
63231-63-0 (RNA)
تواريخ الأحداث: Date Created: 20240125 Date Completed: 20240306 Latest Revision: 20240307
رمز التحديث: 20240307
مُعرف محوري في PubMed: PMC10912769
DOI: 10.1038/s44320-024-00013-0
PMID: 38273160
قاعدة البيانات: MEDLINE
الوصف
تدمد:1744-4292
DOI:10.1038/s44320-024-00013-0