دورية أكاديمية
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Regulation of the Drosophila transcriptome by Pumilio and the CCR4-NOT deadenylase complex.

التفاصيل البيبلوغرافية
العنوان: Regulation of the Drosophila transcriptome by Pumilio and the CCR4-NOT deadenylase complex.
المؤلفون: Haugen RJ; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA., Barnier C; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA., Elrod ND; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77550, USA., Luo H; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5G 1M1, Canada., Jensen MK; Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA., Ji P; Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA., Smibert CA; Department of Biochemistry, University of Toronto, Toronto, Ontario M5G 1M1, Canada., Lipshitz HD; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5G 1M1, Canada., Wagner EJ; Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA., Freddolino PL; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.; Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA., Goldstrohm AC; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA agoldstr@umn.edu.
المصدر: RNA (New York, N.Y.) [RNA] 2024 Jun 17; Vol. 30 (7), pp. 866-890. Date of Electronic Publication: 2024 Jun 17.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 9509184 Publication Model: Electronic Cited Medium: Internet ISSN: 1469-9001 (Electronic) Linking ISSN: 13558382 NLM ISO Abbreviation: RNA Subsets: MEDLINE
أسماء مطبوعة: Publication: <2003->: Cold Spring Harbor, NY : Cold Spring Harbor Laboratory Press
Original Publication: New York, NY : Cambridge University Press, c1995-
مواضيع طبية MeSH: Drosophila Proteins*/genetics , Drosophila Proteins*/metabolism , RNA-Binding Proteins*/metabolism , RNA-Binding Proteins*/genetics , Transcriptome*, Animals ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Ribonucleases/metabolism ; Ribonucleases/genetics ; Gene Expression Regulation, Developmental ; Binding Sites ; Protein Binding ; Drosophila/genetics ; Drosophila/metabolism
مستخلص: The sequence-specific RNA-binding protein Pumilio (Pum) controls Drosophila development; however, the network of mRNAs that it regulates remains incompletely characterized. In this study, we use knockdown and knockout approaches coupled with RNA-seq to measure the impact of Pum on the transcriptome of Drosophila cells in culture. We also use an improved RNA coimmunoprecipitation method to identify Pum-bound mRNAs in Drosophila embryos. Integration of these data sets with the locations of Pum-binding motifs across the transcriptome reveals novel direct Pum target genes involved in neural, muscle, wing, and germ cell development and in cellular proliferation. These genes include components of Wnt, TGF-β, MAPK/ERK, and Notch signaling pathways, DNA replication, and lipid metabolism. We identify the mRNAs regulated by the CCR4-NOT deadenylase complex, a key factor in Pum-mediated repression, and observe concordant regulation of Pum:CCR4-NOT target mRNAs. Computational modeling reveals that Pum binding, binding site number, clustering, and sequence context are important determinants of regulation. In contrast, we show that the responses of direct mRNA targets to Pum-mediated repression are not influenced by the content of optimal synonymous codons. Moreover, contrary to a prevailing model, we do not detect a role for CCR4-NOT in the degradation of mRNAs with low codon optimality. Together, the results of this work provide new insights into the Pum regulatory network and mechanisms and the parameters that influence the efficacy of Pum-mediated regulation.
(© 2024 Haugen et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)
التعليقات: Update of: bioRxiv. 2023 Aug 30:2023.08.29.555372. doi: 10.1101/2023.08.29.555372. (PMID: 37693497)
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معلومات مُعتمدة: R01 GM105707 United States GM NIGMS NIH HHS; R35 GM128637 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: CCR4–NOT; Pumilio; RNA-binding proteins; deadenylase; repression
المشرفين على المادة: 0 (Drosophila Proteins)
0 (RNA-Binding Proteins)
0 (pum protein, Drosophila)
EC 3.1.- (CCR4 protein, Drosophila)
0 (RNA, Messenger)
EC 3.1.- (Ribonucleases)
0 (NOT1 protein, Drosophila)
تواريخ الأحداث: Date Created: 20240416 Date Completed: 20240617 Latest Revision: 20240702
رمز التحديث: 20240702
مُعرف محوري في PubMed: PMC11182014
DOI: 10.1261/rna.079813.123
PMID: 38627019
قاعدة البيانات: MEDLINE
الوصف
تدمد:1469-9001
DOI:10.1261/rna.079813.123