Abstract
Poly(A) tails are critical for mRNA stability and translation. However, recent studies have challenged this view, showing that poly(A) tail length and translation efficiency are decoupled in non-embryonic cells. Using TAIL-seq and ribosome profiling, we investigate poly(A) tail dynamics and translational control in the somatic cell cycle. We find dramatic changes in poly(A) tail lengths of cell-cycle regulatory genes like CDK1, TOP2A, and FBXO5, explaining their translational repression in M phase. We also find that poly(A) tail length is coupled to translation when the poly(A) tail is <20 nucleotides. However, as most genes have >20 nucleotide poly(A) tails, their translation is regulated mainly via poly(A) tail length-independent mechanisms during the cell cycle. Specifically, we find that terminal oligopyrimidine (TOP) tract-containing transcripts escape global translational suppression in M phase and are actively translated. Our quantitative and comprehensive data provide a revised view of translational control in the somatic cell cycle.
Copyright © 2016 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Neoplasm / biosynthesis
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Antigens, Neoplasm / genetics
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CDC2 Protein Kinase
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Cell Cycle Proteins / biosynthesis
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Cell Cycle Proteins / genetics
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Cyclin-Dependent Kinases / biosynthesis
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Cyclin-Dependent Kinases / genetics
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DNA Topoisomerases, Type II / biosynthesis
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DNA Topoisomerases, Type II / genetics
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics
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F-Box Proteins / biosynthesis
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F-Box Proteins / genetics
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Gene Expression Profiling / methods
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Gene Expression Regulation
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Gene Library
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HeLa Cells
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Humans
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M Phase Cell Cycle Checkpoints
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Mitosis*
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Oligodeoxyribonucleotides / genetics
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Oligodeoxyribonucleotides / metabolism
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Poly A / genetics
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Poly A / metabolism*
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Poly dA-dT / genetics
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Poly dA-dT / metabolism
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Poly-ADP-Ribose Binding Proteins
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Protein Biosynthesis*
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RNA Stability
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RNA, Messenger / genetics
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RNA, Messenger / metabolism*
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Ribosomes / metabolism
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S Phase Cell Cycle Checkpoints
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Time Factors
Substances
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Antigens, Neoplasm
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Cell Cycle Proteins
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DNA-Binding Proteins
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F-Box Proteins
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FBXO5 protein, human
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Oligodeoxyribonucleotides
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Poly-ADP-Ribose Binding Proteins
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RNA, Messenger
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oligo (dT) poly (A)
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Poly A
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Poly dA-dT
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CDC2 Protein Kinase
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CDK1 protein, human
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Cyclin-Dependent Kinases
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DNA Topoisomerases, Type II
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TOP2A protein, human