Global Profiling of Cellular Substrates of Human Dcp2
Decapping is the first committed step in 5′-to-3′ RNA decay, and in the cytoplasm of human cells, multiple decapping enzymes regulate the stabilities of distinct subsets of cellular transcripts. However, the complete set of RNAs regulated by any individual decapping enzyme remains incompletely mappe...
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Published in | Biochemistry (Easton) Vol. 59; no. 43; pp. 4176 - 4188 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
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United States
American Chemical Society
03.11.2020
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Abstract | Decapping is the first committed step in 5′-to-3′ RNA decay, and in the cytoplasm of human cells, multiple decapping enzymes regulate the stabilities of distinct subsets of cellular transcripts. However, the complete set of RNAs regulated by any individual decapping enzyme remains incompletely mapped, and no consensus sequence or property is currently known to unambiguously predict decapping enzyme substrates. Dcp2 was the first-identified and best-studied eukaryotic decapping enzyme, but it has been shown to regulate the stability of <400 transcripts in mammalian cells to date. Here, we globally profile changes in the stability of the human transcriptome in Dcp2 knockout cells via TimeLapse-seq. We find that P-body enrichment is the strongest correlate of Dcp2-dependent decay and that modification with m6A exhibits an additive effect with P-body enrichment for Dcp2 targeting. These results are consistent with a model in which P-bodies represent sites where translationally repressed transcripts are sorted for decay by soluble cytoplasmic decay complexes through additional molecular marks. |
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AbstractList | Decapping is the first committed step in 5′-to-3′ RNA decay, and in the cytoplasm of human cells, multiple decapping enzymes regulate the stabilities of distinct subsets of cellular transcripts. However, the complete set of RNAs regulated by any individual decapping enzyme remains incompletely mapped, and no consensus sequence or property is currently known to unambiguously predict decapping enzyme substrates. Dcp2 was the first-identified and best-studied eukaryotic decapping enzyme, but it has been shown to regulate the stability of <400 transcripts in mammalian cells to date. Here, we globally profile changes in the stability of the human transcriptome in Dcp2 knockout cells via TimeLapse-seq. We find that P-body enrichment is the strongest correlate of Dcp2-dependent decay and that modification with m⁶A exhibits an additive effect with P-body enrichment for Dcp2 targeting. These results are consistent with a model in which P-bodies represent sites where translationally repressed transcripts are sorted for decay by soluble cytoplasmic decay complexes through additional molecular marks. Decapping is the first committed step in 5'-to-3' RNA decay, and in the cytoplasm of human cells, multiple decapping enzymes regulate the stabilities of distinct subsets of cellular transcripts. However, the complete set of RNAs regulated by any individual decapping enzyme remains incompletely mapped, and no consensus sequence or property is currently known to unambiguously predict decapping enzyme substrates. Dcp2 was the first-identified and best-studied eukaryotic decapping enzyme, but it has been shown to regulate the stability of <400 transcripts in mammalian cells to date. Here, we globally profile changes in the stability of the human transcriptome in Dcp2 knockout cells via TimeLapse-seq. We find that P-body enrichment is the strongest correlate of Dcp2-dependent decay and that modification with m6A exhibits an additive effect with P-body enrichment for Dcp2 targeting. These results are consistent with a model in which P-bodies represent sites where translationally repressed transcripts are sorted for decay by soluble cytoplasmic decay complexes through additional molecular marks.Decapping is the first committed step in 5'-to-3' RNA decay, and in the cytoplasm of human cells, multiple decapping enzymes regulate the stabilities of distinct subsets of cellular transcripts. However, the complete set of RNAs regulated by any individual decapping enzyme remains incompletely mapped, and no consensus sequence or property is currently known to unambiguously predict decapping enzyme substrates. Dcp2 was the first-identified and best-studied eukaryotic decapping enzyme, but it has been shown to regulate the stability of <400 transcripts in mammalian cells to date. Here, we globally profile changes in the stability of the human transcriptome in Dcp2 knockout cells via TimeLapse-seq. We find that P-body enrichment is the strongest correlate of Dcp2-dependent decay and that modification with m6A exhibits an additive effect with P-body enrichment for Dcp2 targeting. These results are consistent with a model in which P-bodies represent sites where translationally repressed transcripts are sorted for decay by soluble cytoplasmic decay complexes through additional molecular marks. Decapping is the first committed step in 5′-to-3′ RNA decay, and in the cytoplasm of human cells, multiple decapping enzymes regulate the stabilities of distinct subsets of cellular transcripts. However, the complete set of RNAs regulated by any individual decapping enzyme remain incompletely mapped, and no consensus sequence or property is currently known to unambiguously predict decapping enzyme substrates. Dcp2 was the first-identified and best-studied eukaryotic decapping enzyme, but it has been shown to regulate the stability of <400 transcripts in mammalian cells to date. Here, we globally profile changes in stability of the human transcriptome in Dcp2 knockout cells via TimeLapse-seq. We find that P-body enrichment is the strongest correlate of Dcp2-dependent decay, and that modification with m 6 A exhibits an additive effect with P-body enrichment for Dcp2 targeting. These results are consistent with a model in which P-bodies represent sites where translationally repressed transcripts are sorted for decay by soluble cytoplasmic decay complexes through additional molecular marks. Decapping is the first committed step in 5'-to-3' RNA decay, and in the cytoplasm of human cells, multiple decapping enzymes regulate the stabilities of distinct subsets of cellular transcripts. However, the complete set of RNAs regulated by any individual decapping enzyme remains incompletely mapped, and no consensus sequence or property is currently known to unambiguously predict decapping enzyme substrates. Dcp2 was the first-identified and best-studied eukaryotic decapping enzyme, but it has been shown to regulate the stability of <400 transcripts in mammalian cells to date. Here, we globally profile changes in the stability of the human transcriptome in Dcp2 knockout cells via TimeLapse-seq. We find that P-body enrichment is the strongest correlate of Dcp2-dependent decay and that modification with m A exhibits an additive effect with P-body enrichment for Dcp2 targeting. These results are consistent with a model in which P-bodies represent sites where translationally repressed transcripts are sorted for decay by soluble cytoplasmic decay complexes through additional molecular marks. Decapping is the first committed step in 5′-to-3′ RNA decay, and in the cytoplasm of human cells, multiple decapping enzymes regulate the stabilities of distinct subsets of cellular transcripts. However, the complete set of RNAs regulated by any individual decapping enzyme remains incompletely mapped, and no consensus sequence or property is currently known to unambiguously predict decapping enzyme substrates. Dcp2 was the first-identified and best-studied eukaryotic decapping enzyme, but it has been shown to regulate the stability of <400 transcripts in mammalian cells to date. Here, we globally profile changes in the stability of the human transcriptome in Dcp2 knockout cells via TimeLapse-seq. We find that P-body enrichment is the strongest correlate of Dcp2-dependent decay and that modification with m6A exhibits an additive effect with P-body enrichment for Dcp2 targeting. These results are consistent with a model in which P-bodies represent sites where translationally repressed transcripts are sorted for decay by soluble cytoplasmic decay complexes through additional molecular marks. |
Author | Schofield, Jeremy A Luo, Yang Slavoff, Sarah A Simon, Matthew D |
AuthorAffiliation | Department of Chemistry Chemical Biology Institute Department of Molecular Biophysics and Biochemistry |
AuthorAffiliation_xml | – name: Chemical Biology Institute – name: Department of Molecular Biophysics and Biochemistry – name: Department of Chemistry – name: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06529, United States – name: Chemical Biology Institute, Yale University, West Haven, Connecticut 06516, United States – name: Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States |
Author_xml | – sequence: 1 givenname: Yang orcidid: 0000-0002-8709-0103 surname: Luo fullname: Luo, Yang organization: Chemical Biology Institute – sequence: 2 givenname: Jeremy A surname: Schofield fullname: Schofield, Jeremy A organization: Department of Molecular Biophysics and Biochemistry – sequence: 3 givenname: Matthew D orcidid: 0000-0001-7423-5265 surname: Simon fullname: Simon, Matthew D organization: Department of Molecular Biophysics and Biochemistry – sequence: 4 givenname: Sarah A orcidid: 0000-0002-4443-2070 surname: Slavoff fullname: Slavoff, Sarah A email: sarah.slavoff@yale.edu organization: Department of Molecular Biophysics and Biochemistry |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Y.L. designed and performed experiments and data analysis and wrote the manuscript. J.A.S. performed the TimeLapse-seq experiment and data analysis and wrote the manuscript. M.D.S. and S.A.S conceived the project, designed experiments and edited the manuscript. All authors have given approval to the final version of the manuscript. Author Contributions These authors contributed equally |
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Snippet | Decapping is the first committed step in 5′-to-3′ RNA decay, and in the cytoplasm of human cells, multiple decapping enzymes regulate the stabilities of... Decapping is the first committed step in 5'-to-3' RNA decay, and in the cytoplasm of human cells, multiple decapping enzymes regulate the stabilities of... |
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SubjectTerms | additive effect Animals cells consensus sequence cytoplasm Cytoplasm - genetics Cytoplasm - metabolism deterioration Endoribonucleases - genetics Endoribonucleases - metabolism enzyme substrates enzymes exhibitions Humans Models, Biological RNA RNA Stability - genetics RNA Stability - physiology transcriptome Transcriptome - genetics Transcriptome - physiology translation (genetics) |
Title | Global Profiling of Cellular Substrates of Human Dcp2 |
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