Treffer: RBBP6 anchors pre-mRNA 3' end processing to nuclear speckles for efficient gene expression.
Title:
RBBP6 anchors pre-mRNA 3' end processing to nuclear speckles for efficient gene expression.
Authors:
Yoon Y; Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA., Bournique E; Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA., Soles LV; Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA., Yin H; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA., Chu HF; Department of Biological Sciences, Columbia University, New York, NY 10027, USA., Yin C; Department of Electrical and Computer Engineering, University of Washington, Seattle, Seattle, WA 98195, USA., Zhuang Y; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA., Liu X; Department of Biological Sciences, Columbia University, New York, NY 10027, USA., Liu L; Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA., Jeong J; Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA., Yu C; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA., Valdez M; Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA., Tian L; Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA., Huang L; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA., Shi X; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA; Department of Chemistry, University of California, Irvine, Irvine, CA 92697, USA., Seelig G; Department of Electrical and Computer Engineering, University of Washington, Seattle, Seattle, WA 98195, USA; Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, Seattle, WA 98195, USA., Ding F; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA., Tong L; Department of Biological Sciences, Columbia University, New York, NY 10027, USA., Buisson R; Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA., Shi Y; Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: yongshes@uci.edu.
Source:
Molecular cell [Mol Cell] 2025 Feb 06; Vol. 85 (3), pp. 555-570.e8. Date of Electronic Publication: 2025 Jan 10.
Publication Type:
Journal Article
Language:
English
Journal Info:
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
Imprint Name(s):
Publication: Cambridge Ma : Cell Press
Original Publication: Cambridge, Mass. : Cell Press, c1997-
Original Publication: Cambridge, Mass. : Cell Press, c1997-
MeSH Terms:
RNA Precursors*/genetics , RNA Precursors*/metabolism , Cell Nucleus*/metabolism , Cell Nucleus*/genetics , RNA 3' End Processing* , RNA, Messenger*/genetics , RNA, Messenger*/metabolism, Humans ; HeLa Cells ; RNA Splicing ; RNA Polymerase II/metabolism ; RNA Polymerase II/genetics ; HEK293 Cells ; Protein Binding ; Intrinsically Disordered Proteins/metabolism ; Intrinsically Disordered Proteins/genetics ; RNA Processing, Post-Transcriptional ; Gene Expression Regulation ; RNA-Binding Proteins/metabolism ; RNA-Binding Proteins/genetics
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Mol Cell. 2009 Feb 13;33(3):365-76. (PMID: 19217410)
Nucleic Acids Res. 2006;34(22):e148. (PMID: 17142220)
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RNA. 2000 Sep;6(9):1197-211. (PMID: 10999598)
Nat Methods. 2012 Jul;9(7):671-5. (PMID: 22930834)
J Cell Sci. 2022 Jul 1;135(13):. (PMID: 35788677)
J Cell Sci. 1999 Dec;112 ( Pt 24):4651-61. (PMID: 10574713)
Genes Dev. 2022 Feb 1;36(3-4):195-209. (PMID: 35177537)
Sci Adv. 2024 Oct 18;10(42):eadp7727. (PMID: 39413186)
Proc Natl Acad Sci U S A. 2012 Nov 13;109(46):18773-8. (PMID: 23112178)
Nat Struct Mol Biol. 2019 Jun;26(6):424-432. (PMID: 31133700)
EMBO J. 2002 Jun 3;21(11):2664-71. (PMID: 12032079)
Mol Biol Evol. 2004 May;21(5):841-50. (PMID: 14963095)
Nat Commun. 2015 May 20;6:7126. (PMID: 25989971)
Mol Biol Cell. 2007 Apr;18(4):1282-92. (PMID: 17267687)
Wiley Interdiscip Rev RNA. 2011 May-Jun;2(3):321-35. (PMID: 21957020)
Nat Rev Mol Cell Biol. 2023 Apr;24(4):288-304. (PMID: 36424481)
Science. 2020 Feb 7;367(6478):700-703. (PMID: 32029631)
RNA Biol. 2017 Jun 3;14(6):726-738. (PMID: 28059623)
J Cell Biol. 2020 Sep 7;219(9):. (PMID: 32609799)
Nat Struct Mol Biol. 2023 Dec;30(12):1947-1957. (PMID: 38087090)
Nature. 1990 Feb 1;343(6257):437-41. (PMID: 2137203)
Nature. 2019 Aug;572(7770):543-548. (PMID: 31391587)
Genes Dev. 2014 Oct 15;28(20):2248-60. (PMID: 25319826)
Genes Dev. 2011 Sep 1;25(17):1770-82. (PMID: 21896654)
J Biol Chem. 2023 Apr;299(4):103047. (PMID: 36822327)
Nucleic Acids Res. 2018 Jul 2;46(W1):W329-W337. (PMID: 29860432)
Elife. 2020 Oct 23;9:. (PMID: 33095160)
Nucleic Acids Res. 2022 Aug 26;50(15):8599-8614. (PMID: 35929045)
Development. 2018 Jun 26;145(12):. (PMID: 29945988)
Mol Biol Cell. 2004 Aug;15(8):3876-90. (PMID: 15169873)
Cell. 2018 Jul 26;174(3):744-757.e24. (PMID: 29887377)
Cell. 2021 Nov 11;184(23):5775-5790.e30. (PMID: 34739832)
Mol Cell. 2021 Apr 15;81(8):1666-1681.e6. (PMID: 33823140)
PLoS Genet. 2013;9(7):e1003613. (PMID: 23874216)
EMBO J. 2014 Apr 16;33(8):878-89. (PMID: 24596251)
Nat Rev Mol Cell Biol. 2017 Jan;18(1):18-30. (PMID: 27677860)
Oncogene. 1997 Jan 16;14(2):145-55. (PMID: 9010216)
Bioessays. 2016 Dec;38(12):1197-1208. (PMID: 27767214)
Cold Spring Harb Perspect Biol. 2022 Jul 1;14(7):. (PMID: 34400557)
Science. 1993 Feb 26;259(5099):1330-5. (PMID: 8446902)
J Cell Biol. 2018 Nov 5;217(11):4025-4048. (PMID: 30154186)
Curr Biol. 2014 May 19;24(10):1138-44. (PMID: 24794297)
Nat Commun. 2020 Jan 15;11(1):293. (PMID: 31941886)
Mol Cell Biol. 2001 Dec;21(24):8346-56. (PMID: 11713271)
Genome Biol. 2022 Nov 5;23(1):232. (PMID: 36335397)
PLoS Genet. 2021 Mar 8;17(3):e1009263. (PMID: 33684133)
Cell. 2019 Jul 11;178(2):473-490.e26. (PMID: 31230715)
Genomics. 1995 Jun 10;27(3):511-9. (PMID: 7558034)
Curr Opin Cell Biol. 1999 Jun;11(3):358-62. (PMID: 10395560)
Genes Dev. 1997 Nov 1;11(21):2755-66. (PMID: 9353246)
Nucleic Acids Res. 2017 Oct 13;45(18):10350-10368. (PMID: 28977640)
RNA. 2011 Apr;17(4):761-72. (PMID: 21343387)
Proc Int Conf Intell Syst Mol Biol. 1994;2:28-36. (PMID: 7584402)
Genes Dev. 2022 Feb 1;36(3-4):210-224. (PMID: 35177536)
Aging Cell. 2020 Oct;19(10):e13215. (PMID: 32813328)
EMBO J. 1996 Jun 3;15(11):2883-92. (PMID: 8654386)
RNA. 2012 Dec;18(12):2105-17. (PMID: 23097429)
Nature. 2024 May;629(8014):1165-1173. (PMID: 38720076)
Cold Spring Harb Perspect Biol. 2011 Feb 01;3(2):. (PMID: 20926517)
Cell Rep. 2024 Mar 26;43(3):113827. (PMID: 38381607)
Nat Protoc. 2016 Jan;11(1):118-33. (PMID: 26678082)
Curr Protoc Chem Biol. 2016 Dec 7;8(4):234-250. (PMID: 27925666)
Trends Cell Biol. 2016 Mar;26(3):227-237. (PMID: 26597575)
Trends Cell Biol. 2024 Jul;34(7):595-605. (PMID: 37993310)
Nat Chem Biol. 2018 May;14(5):431-441. (PMID: 29581585)
Mol Cell. 2022 Mar 3;82(5):1035-1052.e9. (PMID: 35182477)
Bioinformatics. 2010 Jan 1;26(1):139-40. (PMID: 19910308)
Nucleic Acids Res. 2019 May 7;47(8):e47. (PMID: 30783653)
Mol Cell Biol. 2014 Nov;34(21):3955-67. (PMID: 25135474)
Curr Opin Genet Dev. 2019 Apr;55:91-99. (PMID: 31394307)
EMBO J. 1999 Aug 2;18(15):4308-20. (PMID: 10428969)
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517)
Methods Enzymol. 2021;655:25-35. (PMID: 34183125)
Nat Chem Biol. 2007 Sep;3(9):570-5. (PMID: 17643112)
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W401-7. (PMID: 24861617)
FEBS J. 2022 Nov;289(22):7234-7245. (PMID: 34245118)
Cold Spring Harb Perspect Biol. 2011 Jul 01;3(7):. (PMID: 21441581)
Gene. 2007 Jul 15;396(2):373-90. (PMID: 17531405)
iScience. 2018 Jun 29;4:204-215. (PMID: 30240742)
Annu Rev Biochem. 2023 Jun 20;92:199-225. (PMID: 37001138)
J Cell Sci. 2020 Feb 21;133(4):. (PMID: 31988151)
Genomics. 1995 Nov 1;30(1):98-101. (PMID: 8595913)
Mol Cell. 2009 Feb 13;33(3):365-76. (PMID: 19217410)
Nucleic Acids Res. 2006;34(22):e148. (PMID: 17142220)
Genome Res. 2021 Feb;31(2):251-264. (PMID: 33355299)
RNA. 2000 Sep;6(9):1197-211. (PMID: 10999598)
Nat Methods. 2012 Jul;9(7):671-5. (PMID: 22930834)
J Cell Sci. 2022 Jul 1;135(13):. (PMID: 35788677)
J Cell Sci. 1999 Dec;112 ( Pt 24):4651-61. (PMID: 10574713)
Genes Dev. 2022 Feb 1;36(3-4):195-209. (PMID: 35177537)
Sci Adv. 2024 Oct 18;10(42):eadp7727. (PMID: 39413186)
Proc Natl Acad Sci U S A. 2012 Nov 13;109(46):18773-8. (PMID: 23112178)
Nat Struct Mol Biol. 2019 Jun;26(6):424-432. (PMID: 31133700)
EMBO J. 2002 Jun 3;21(11):2664-71. (PMID: 12032079)
Mol Biol Evol. 2004 May;21(5):841-50. (PMID: 14963095)
Nat Commun. 2015 May 20;6:7126. (PMID: 25989971)
Grant Information:
R21 AI185033 United States AI NIAID NIH HHS; DP2 GM150017 United States GM NIGMS NIH HHS; R35 GM149294 United States GM NIGMS NIH HHS; R21 ES036190 United States ES NIEHS NIH HHS; P30 CA062203 United States CA NCI NIH HHS; R35 GM118093 United States GM NIGMS NIH HHS; R37 CA252081 United States CA NCI NIH HHS; R01 AI170840 United States AI NIAID NIH HHS; S10 OD032327 United States OD NIH HHS; R35 GM145249 United States GM NIGMS NIH HHS
Contributed Indexing:
Keywords: biomolecular condensate; cleavage and polyadenylation; gene expression; intrinsically disordered region; membraneless organelle; nuclear speckle; phase separation; pre-mRNA 3′ end processing; transcription termination
Substance Nomenclature:
0 (RNA Precursors)
EC 2.7.7.- (RNA Polymerase II)
0 (RNA, Messenger)
0 (Intrinsically Disordered Proteins)
0 (RNA-Binding Proteins)
EC 2.7.7.- (RNA Polymerase II)
0 (RNA, Messenger)
0 (Intrinsically Disordered Proteins)
0 (RNA-Binding Proteins)
Entry Date(s):
Date Created: 20250111 Date Completed: 20250430 Latest Revision: 20250722
Update Code:
20250722
PubMed Central ID:
PMC11805622
DOI:
10.1016/j.molcel.2024.12.016
PMID:
39798570
Database:
MEDLINE
Weitere Informationen
Pre-mRNA 3' processing is an integral step in mRNA biogenesis. However, where this process occurs in the nucleus remains unknown. Here, we demonstrate that nuclear speckles (NSs), membraneless organelles enriched with splicing factors, are major sites for pre-mRNA 3' processing in human cells. We show that the essential pre-mRNA 3' processing factor retinoblastoma-binding protein 6 (RBBP6) associates strongly with NSs via its C-terminal intrinsically disordered region (IDR). Importantly, although the conserved N-terminal domain (NTD) of RBBP6 is sufficient for pre-mRNA 3' processing in vitro, its IDR-mediated association with NSs is required for efficient pre-mRNA 3' processing in cells. Through proximity labeling analyses, we provide evidence that pre-mRNA 3' processing for over 50% of genes occurs near NSs. We propose that NSs serve as hubs for RNA polymerase II transcription, pre-mRNA splicing, and 3' processing, thereby enhancing the efficiency and coordination of different gene expression steps.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Declaration of interests The authors declare no competing interests.