Regulation of Poly(A) Tail and Translation during the Somatic Cell Cycle.

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.

[1]  S. Mukherjee,et al.  Increased phosphorylation of eukaryotic initiation factor 2alpha at the G2/M boundary in human osteosarcoma cells correlates with deglycosylation of p67 and a decreased rate of protein synthesis. , 1999, Experimental cell research.

[2]  R. Kornberg,et al.  Repeating structure of cytoplasmic poly(A)-ribonucleoprotein. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[3]  D. Bartel,et al.  Poly(A)-tail profiling reveals an embryonic switch in translational control , 2014, Nature.

[4]  P. Sarnow,et al.  Preferential Translation of Internal Ribosome Entry Site-containing mRNAs during the Mitotic Cycle in Mammalian Cells* , 2004, Journal of Biological Chemistry.

[5]  T. Gant,et al.  A novel method for poly(A) fractionation reveals a large population of mRNAs with a short poly(A) tail in mammalian cells , 2007, Nucleic acids research.

[6]  F. Amaldi,et al.  TOP genes: a translationally controlled class of genes including those coding for ribosomal proteins. , 1997, Progress in molecular and subcellular biology.

[7]  K. Nakai,et al.  Comprehensive detection of human terminal oligo-pyrimidine (TOP) genes and analysis of their characteristics , 2008, Nucleic acids research.

[8]  Sonja J. Prohaska,et al.  The CHR site: definition and genome-wide identification of a cell cycle transcriptional element , 2014, Nucleic acids research.

[9]  Tamar Geiger,et al.  Novel proteomic approach (PUNCH-P) reveals cell cycle-specific fluctuations in mRNA translation , 2013, Genes & development.

[10]  A. Sachs.  Cell Cycle–Dependent Translation Initiation IRES Elements Prevail , 2000, Cell.

[11]  Michael J. Emanuele,et al.  A proteomic chronology of gene expression through the cell cycle in human myeloid leukemia cells , 2014, eLife.

[12]  J. Weissman,et al.  Regulation of mRNA translation during mitosis , 2015, eLife.

[13]  D. Prescott,et al.  Synthesis of RNA and protein during mitosis in mammalian tissue culture cells. , 1962, Experimental cell research.

[14]  Joel D. Richter,et al.  Cytoplasmic Polyadenylation in Development and Beyond , 1999, Microbiology and Molecular Biology Reviews.

[15]  N. Sonenberg,et al.  Suppression of cap-dependent translation in mitosis. , 2001, Genes & development.

[16]  C. Ball,et al.  Identification of genes periodically expressed in the human cell cycle and their expression in tumors. , 2002, Molecular biology of the cell.

[17]  Felice-Alessio Bava,et al.  Translational control by changes in poly(A) tail length: recycling mRNAs , 2012, Nature Structural &Molecular Biology.

[18]  J. Celis,et al.  Increased phosphorylation of elongation factor 2 during mitosis in transformed human amnion cells correlates with a decreased rate of protein synthesis. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Davide Ruggero,et al.  Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency , 2008, Nature.

[20]  J. Cook,et al.  Cell Cycle-Regulated Protein Abundance Changes in Synchronously Proliferating HeLa Cells Include Regulation of Pre-mRNA Splicing Proteins , 2013, PloS one.

[21]  Yoosik Kim,et al.  PKR is activated by cellular dsRNAs during mitosis and acts as a mitotic regulator , 2014, Genes & development.

[22]  S. Brunak,et al.  Quantitative Phosphoproteomics Reveals Widespread Full Phosphorylation Site Occupancy During Mitosis , 2010, Science Signaling.

[23]  P. Moore,et al.  CDK1 substitutes for mTOR kinase to activate mitotic cap-dependent protein translation , 2015, Proceedings of the National Academy of Sciences.

[24]  C. Baglioni,et al.  Regulation of protein synthesis in mitotic HeLa cells , 1979, Journal of cellular physiology.

[25]  J. Rappsilber,et al.  Proteomics of isolated mitotic chromosomes identifies the kinetochore protein Ska3/Rama1. , 2010, Cold Spring Harbor symposia on quantitative biology.

[26]  Javier Gallego,et al.  Mitotic cell-cycle progression is regulated by CPEB1 and CPEB4-dependent translational control , 2010, Nature Cell Biology.

[27]  Hua Tang,et al.  Amino Acid-Induced Translation of TOP mRNAs Is Fully Dependent on Phosphatidylinositol 3-Kinase-Mediated Signaling, Is Partially Inhibited by Rapamycin, and Is Independent of S6K1 and rpS6 Phosphorylation , 2001, Molecular and Cellular Biology.

[28]  O. Elroy-Stein,et al.  DAP5 promotes cap-independent translation of Bcl-2 and CDK1 to facilitate cell survival during mitosis. , 2008, Molecular cell.

[29]  V. Kim,et al.  TAIL-seq: genome-wide determination of poly(A) tail length and 3' end modifications. , 2014, Molecular cell.

[30]  M. Kirschner,et al.  Profiling of Ubiquitin-like Modifications Reveals Features of Mitotic Control , 2013, Cell.

[31]  N. Sonenberg,et al.  A cell cycle-dependent internal ribosome entry site. , 2000, Molecular cell.

[32]  Tammara A. Wood,et al.  Identification of cell cycle–regulated genes periodically expressed in U2OS cells and their regulation by FOXM1 and E2F transcription factors , 2013, Molecular biology of the cell.

[33]  T. Wassmer,et al.  SNX4 coordinates endosomal sorting of TfnR with dynein-mediated transport into the endocytic recycling compartment , 2007, Nature Cell Biology.

[34]  J. Pines,et al.  Cyclin a Is Destroyed in Prometaphase and Can Delay Chromosome Alignment and Anaphase , 2001, The Journal of cell biology.

[35]  Jyoti S Choudhary,et al.  Quantitative proteomics reveals the basis for the biochemical specificity of the cell-cycle machinery. , 2011, Molecular cell.

[36]  P. Sharp,et al.  14-3-3sigma controls mitotic translation to facilitate cytokinesis. , 2007, Nature.

[37]  Q. Cao,et al.  Translational Control of the Embryonic Cell Cycle , 2002, Cell.

[38]  P. Sharp,et al.  14-3-3σ controls mitotic translation to facilitate cytokinesis , 2007, Nature.

[39]  Adam B. Olshen,et al.  The translational landscape of the mammalian cell cycle. , 2013, Molecular cell.

[40]  Ronald W. Davis,et al.  A single domain of yeast poly(A)-binding protein is necessary and sufficient for RNA binding and cell viability , 1987, Molecular and cellular biology.

[41]  D. Sabatini,et al.  A unifying model for mTORC1-mediated regulation of mRNA translation , 2012, Nature.

[42]  Ronald W. Davis,et al.  Transcriptional regulation and function during the human cell cycle , 2001, Nature Genetics.