دورية أكاديمية
أعرض في EDS

The splicing factor CCAR1 regulates the Fanconi anemia/BRCA pathway.

التفاصيل البيبلوغرافية
العنوان: The splicing factor CCAR1 regulates the Fanconi anemia/BRCA pathway.
المؤلفون: Harada N; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA., Asada S; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA., Jiang L; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA., Nguyen H; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA., Moreau L; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA., Marina RJ; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA., Adelman K; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA., Iyer DR; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: divyar_iyer@dfci.harvard.edu., D'Andrea AD; Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: alan_dandrea@dfci.harvard.edu.
المصدر: Molecular cell [Mol Cell] 2024 Jul 25; Vol. 84 (14), pp. 2618-2633.e10. Date of Electronic Publication: 2024 Jul 17.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 9802571 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4164 (Electronic) Linking ISSN: 10972765 NLM ISO Abbreviation: Mol Cell Subsets: MEDLINE
أسماء مطبوعة: Publication: Cambridge Ma : Cell Press
Original Publication: Cambridge, Mass. : Cell Press, c1997-
مواضيع طبية MeSH: Fanconi Anemia*/genetics , Fanconi Anemia*/metabolism , Fanconi Anemia Complementation Group A Protein*/genetics , Fanconi Anemia Complementation Group A Protein*/metabolism , RNA Splicing* , Splicing Factor U2AF*/metabolism , Splicing Factor U2AF*/genetics , Cell Cycle Proteins*/genetics , Cell Cycle Proteins*/metabolism , Apoptosis Regulatory Proteins*/genetics , Apoptosis Regulatory Proteins*/metabolism, Humans ; BRCA1 Protein/metabolism ; BRCA1 Protein/genetics ; BRCA2 Protein/metabolism ; BRCA2 Protein/genetics ; DNA Repair ; Endodeoxyribonucleases ; Exons ; HEK293 Cells ; HeLa Cells ; Protein Binding ; RNA Precursors/metabolism ; RNA Precursors/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Signal Transduction ; Spliceosomes/metabolism ; Spliceosomes/genetics
مستخلص: The twenty-three Fanconi anemia (FA) proteins cooperate in the FA/BRCA pathway to repair DNA interstrand cross-links (ICLs). The cell division cycle and apoptosis regulator 1 (CCAR1) protein is also a regulator of ICL repair, though its possible function in the FA/BRCA pathway remains unknown. Here, we demonstrate that CCAR1 plays a unique upstream role in the FA/BRCA pathway and is required for FANCA protein expression in human cells. Interestingly, CCAR1 co-immunoprecipitates with FANCA pre-mRNA and is required for FANCA mRNA processing. Loss of CCAR1 results in retention of a poison exon in the FANCA transcript, thereby leading to reduced FANCA protein expression. A unique domain of CCAR1, the EF hand domain, is required for interaction with the U2AF heterodimer of the spliceosome and for excision of the poison exon. Taken together, CCAR1 is a splicing modulator required for normal splicing of the FANCA mRNA and other mRNAs involved in various cellular pathways.
Competing Interests: Declaration of interests A.D.D. reports consulting for AbbVie, Deerfield Management Company, Impact Therapeutics, Moderna Therapeutics, PrimeFour Therapeutics, Schrödinger Inc., Servier BioInnovation LLC, and Tango Therapeutics; is a Scientific Advisory Board Member and Stockholder for Impact Therapeutics and Covant Therapeutics. K.A. is a member of the Advisory Board of Molecular Cell, the SAB of CAMP4 Therapeutics, consults for Syros Pharmaceuticals and Odyssey Therapeutics, and received research funding from Novartis not related to this work.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
References: Nat Rev Mol Cell Biol. 2016 Jun;17(6):337-49. (PMID: 27145721)
Mol Cells. 2015 Aug;38(8):669-76. (PMID: 26194820)
Cancers (Basel). 2019 Feb 14;11(2):. (PMID: 30769864)
Cell Cycle. 2008 May 15;7(10):1467-72. (PMID: 18418069)
Nucleic Acids Res. 2022 May 6;50(8):4685-4702. (PMID: 35438785)
Nat Rev Cancer. 2018 Mar;18(3):168-185. (PMID: 29376519)
Nat Methods. 2014 Aug;11(8):783-784. (PMID: 25075903)
Bioinformatics. 2013 Jan 1;29(1):15-21. (PMID: 23104886)
Biomed Res Int. 2014;2014:418458. (PMID: 25610865)
Nat Struct Mol Biol. 2018 May;25(5):357-364. (PMID: 29662218)
Genome Res. 2015 Jan;25(1):14-26. (PMID: 25267526)
Genetics. 2022 Sep 30;222(2):. (PMID: 36040194)
Curr Opin Struct Biol. 2000 Dec;10(6):637-43. (PMID: 11114499)
Nature. 2012 Mar 25;484(7394):386-9. (PMID: 22446626)
J Biol Chem. 2020 Dec 11;295(50):17148-17157. (PMID: 33020180)
Am Soc Clin Oncol Educ Book. 2019 Jan;39:185-195. (PMID: 31099635)
Cell. 2011 Mar 4;144(5):646-74. (PMID: 21376230)
J Cell Sci. 2018 Jun 11;131(11):. (PMID: 29748380)
Trends Biochem Sci. 2000 Mar;25(3):112-4. (PMID: 10694879)
J Biol Chem. 2022 Aug;298(8):102268. (PMID: 35850305)
J Biol Chem. 2014 Jun 13;289(24):17078-86. (PMID: 24811171)
Proc Natl Acad Sci U S A. 2022 Dec 6;119(49):e2214935119. (PMID: 36442094)
Nucleic Acids Res. 2021 Jan 8;49(D1):D916-D923. (PMID: 33270111)
J Am Soc Mass Spectrom. 1994 Nov;5(11):976-89. (PMID: 24226387)
Exp Hematol. 1999 Apr;27(4):587-93. (PMID: 10210316)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Nat Biotechnol. 2016 May;34(5):525-7. (PMID: 27043002)
Nat Biotechnol. 2022 Jul;40(7):1103-1113. (PMID: 35241838)
Nucleic Acids Res. 2015 Apr 20;43(7):e47. (PMID: 25605792)
Oncotarget. 2015 Mar 30;6(9):6499-510. (PMID: 25894788)
Nat Methods. 2010 Dec;7(12):1009-15. (PMID: 21057496)
Mol Cancer. 2023 May 12;22(1):83. (PMID: 37173708)
Oncogene. 2005 Jul 21;24(31):4908-20. (PMID: 15824730)
Nature. 2013 Jan 17;493(7432):356-63. (PMID: 23325218)
F1000Res. 2015 Dec 30;4:1521. (PMID: 26925227)
J Biol Chem. 2009 Jul 31;284(31):20629-37. (PMID: 19520846)
Genome Res. 2003 Nov;13(11):2498-504. (PMID: 14597658)
Nature. 2015 Feb 12;518(7538):258-62. (PMID: 25642963)
Bioinformatics. 2010 Jan 1;26(1):139-40. (PMID: 19910308)
J Mass Spectrom. 2001 Oct;36(10):1083-91. (PMID: 11747101)
Trends Cell Biol. 2016 Jan;26(1):52-64. (PMID: 26437586)
RNA Biol. 2024 Jan;21(1):1-11. (PMID: 38126797)
FEBS J. 2021 Jul;288(14):4382-4393. (PMID: 33511782)
Mol Cell. 2012 Feb 24;45(4):567-80. (PMID: 22365833)
Mol Cell. 2020 Feb 6;77(3):461-474.e9. (PMID: 31676232)
Mol Cell. 2014 Oct 2;56(1):90-103. (PMID: 25219497)
Anal Chem. 1996 Mar 1;68(5):850-8. (PMID: 8779443)
Cancer Sci. 2020 Oct;111(10):3416-3425. (PMID: 33403784)
Mol Cell Biol. 2011 Jul;31(13):2667-82. (PMID: 21536652)
Cancer Res. 2022 Oct 17;82(20):3815-3829. (PMID: 35972384)
Mol Cell Biol. 1999 Jul;19(7):4866-73. (PMID: 10373536)
J Biol Chem. 2003 Aug 29;278(35):33422-35. (PMID: 12816952)
Genome Res. 2012 Oct;22(10):2008-17. (PMID: 22722343)
Genes Cancer. 2020 Jul 22;11(3-4):95-105. (PMID: 33488948)
Genome Biol. 2010;11(5):R53. (PMID: 20482850)
Oncogene. 2018 Aug;37(34):4692-4710. (PMID: 29755131)
Mol Cell. 2008 Aug 22;31(4):510-519. (PMID: 18722177)
Mol Cell. 2018 Dec 20;72(6):925-941.e4. (PMID: 30576655)
Annu Rev Cancer Biol. 2019 Mar;3:457-478. (PMID: 30882047)
Blood. 2000 Nov 1;96(9):3224-30. (PMID: 11050007)
Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):E5593-601. (PMID: 25480548)
Nat Cell Biol. 2016 Dec;18(12):1311-1323. (PMID: 27842057)
Cell. 2020 Jul 23;182(2):481-496.e21. (PMID: 32649862)
J Biol Chem. 2011 Nov 4;286(44):38000-38017. (PMID: 21903591)
Nucleic Acids Res. 2021 May 7;49(8):4239-4257. (PMID: 33744950)
معلومات مُعتمدة: P30 CA006516 United States CA NCI NIH HHS; R01 HL052725 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: CCAR1; DNA repair; EF hand; FANCA; Fanconi anemia; U2AF1/2; alternative splicing; poison exon
المشرفين على المادة: 0 (BRCA1 Protein)
0 (BRCA1 protein, human)
0 (BRCA2 Protein)
0 (BRCA2 protein, human)
EC 3.1.- (Endodeoxyribonucleases)
0 (FANCA protein, human)
0 (Fanconi Anemia Complementation Group A Protein)
EC 3.1.- (RBBP8 protein, human)
0 (RNA Precursors)
0 (RNA, Messenger)
0 (Splicing Factor U2AF)
0 (U2AF1 protein, human)
0 (CCAR1 protein, human)
0 (Cell Cycle Proteins)
0 (Apoptosis Regulatory Proteins)
تواريخ الأحداث: Date Created: 20240718 Date Completed: 20240728 Latest Revision: 20240815
رمز التحديث: 20240815
مُعرف محوري في PubMed: PMC11321822
DOI: 10.1016/j.molcel.2024.06.031
PMID: 39025073
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-4164
DOI:10.1016/j.molcel.2024.06.031