دورية أكاديمية
أعرض في EDS

PTBP1 controls intestinal epithelial regeneration through post-transcriptional regulation of gene expression.

التفاصيل البيبلوغرافية
العنوان: PTBP1 controls intestinal epithelial regeneration through post-transcriptional regulation of gene expression.
المؤلفون: Chembazhi UV; Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA., Tung WS; Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA., Hwang H; Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA., Wang Y; Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA., Lalwani A; Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA., Nguyen KL; Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA., Bangru S; Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA., Yee D; Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA., Chin K; Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA., Yang J; Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA., Kalsotra A; Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.; Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA., Mei W; Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA.; Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
المصدر: Nucleic acids research [Nucleic Acids Res] 2023 Mar 21; Vol. 51 (5), pp. 2397-2414.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
مواضيع طبية MeSH: Gene Expression Regulation* , Heterogeneous-Nuclear Ribonucleoproteins*/genetics , Heterogeneous-Nuclear Ribonucleoproteins*/metabolism , Proto-Oncogene Proteins c-akt*/metabolism, Animals ; Mice ; Cell Differentiation ; Polypyrimidine Tract-Binding Protein/genetics ; Polypyrimidine Tract-Binding Protein/metabolism ; Regeneration/genetics ; RNA Splicing
مستخلص: The intestinal epithelial regeneration is driven by intestinal stem cells under homeostatic conditions. Differentiated intestinal epithelial cells, such as Paneth cells, are capable of acquiring multipotency and contributing to regeneration upon the loss of intestinal stem cells. Paneth cells also support intestinal stem cell survival and regeneration. We report here that depletion of an RNA-binding protein named polypyrimidine tract binding protein 1 (PTBP1) in mouse intestinal epithelial cells causes intestinal stem cell death and epithelial regeneration failure. Mechanistically, we show that PTBP1 inhibits neuronal-like splicing programs in intestinal crypt cells, which is critical for maintaining intestinal stem cell stemness. This function is achieved at least in part through promoting the non-productive splicing of its paralog PTBP2. Moreover, PTBP1 inhibits the expression of an AKT inhibitor PHLDA3 in Paneth cells and permits AKT activation, which presumably maintains Paneth cell plasticity and function in supporting intestinal stem cell niche. We show that PTBP1 directly binds to a CU-rich region in the 3' UTR of Phlda3, which we demonstrate to be critical for downregulating the mRNA and protein levels of Phlda3. Our results thus reveal the multifaceted in vivo regulation of intestinal epithelial regeneration by PTBP1 at the post-transcriptional level.
(© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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معلومات مُعتمدة: R01 AA010154 United States AA NIAAA NIH HHS; R03 AI146900 United States AI NIAID NIH HHS; R21 HD104039 United States HD NICHD NIH HHS; R01 GM140306 United States GM NIGMS NIH HHS; R03 AI138138 United States AI NIAID NIH HHS; R01 HL126845 United States HL NHLBI NIH HHS; R35 GM131810 United States GM NIGMS NIH HHS; T32 EB019944 United States EB NIBIB NIH HHS
المشرفين على المادة: 0 (Heterogeneous-Nuclear Ribonucleoproteins)
139076-35-0 (Polypyrimidine Tract-Binding Protein)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
0 (Ptbp1 protein, mouse)
تواريخ الأحداث: Date Created: 20230206 Date Completed: 20230323 Latest Revision: 20230323
رمز التحديث: 20230324
مُعرف محوري في PubMed: PMC10018364
DOI: 10.1093/nar/gkad042
PMID: 36744439
قاعدة البيانات: MEDLINE
الوصف
تدمد:1362-4962
DOI:10.1093/nar/gkad042