Abstract
Understanding the causes and consequences of dynamic changes in the abundance and activity of cellular components during cell division is what most cell cycle studies are about. Here we focus on control of gene expression in the cell cycle at the level of translation. The advent of deep sequencing methodologies led to technologies that quantify the levels of all mRNAs that are bound by ribosomes and engaged in translation in the cell (Ingolia et al. Science 324:218–223, 2009). This approach has been applied recently to synchronous cell populations to find transcripts under translational control at different cell cycle phases (Blank et al. EMBO J 36:487–502, 2017; Stumpf et al. Mol Cell 52:574–582, 2013; Tanenbaum et al. Elife 4:e07957, 2015). These studies revealed new biology, but they also have limitations, pointing to challenges that need to be addressed in the future.
Similar content being viewed by others
References
Albert FW, Muzzey D, Weissman JS, Kruglyak L (2014) Genetic influences on translation in yeast. PLoS Genet 10:e1004692. doi:10.1371/journal.pgen.1004692
Atilla-Gokcumen GE, Muro E, Relat-Goberna J, Sasse S, Bedigian A, Coughlin ML, Garcia-Manyes S, Eggert US (2014) Dividing cells regulate their lipid composition and localization. Cell 156:428–439. doi:10.1016/j.cell.2013.12.015
Banfalvi G (2008) Cell cycle synchronization of animal cells and nuclei by centrifugal elutriation. Nat Protoc 3:663–673. doi:10.1038/nprot.2008.34
Benanti JA (2016) Create, activate, destroy, repeat: Cdk1 controls proliferation by limiting transcription factor activity. Curr Genet 62:271–276. doi:10.1007/s00294-015-0535-5
Blank HM, Perez R, He C, Maitra N, Metz R, Hill J, Lin Y, Johnson CD, Bankaitis VA, Kennedy BK, Aramayo R, Polymenis M (2017) Translational control of lipogenic enzymes in the cell cycle of synchronous, growing yeast cells. EMBO J 36:487–502. doi:10.15252/embj.201695050
Brar GA, Yassour M, Friedman N, Regev A, Ingolia NT, Weissman JS (2012) High-resolution view of the yeast meiotic program revealed by ribosome profiling. Science 335:552–557. doi:10.1126/science.1215110
Burns S, Avena JS, Unruh JR, Yu Z, Smith SE, Slaughter BD, Winey M, Jaspersen SL (2015) Structured illumination with particle averaging reveals novel roles for yeast centrosome components during duplication. Elife. doi:10.7554/eLife.08586
Cho RJ, Campbell MJ, Winzeler EA, Steinmetz L, Conway A, Wodicka L, Wolfsberg TG, Gabrielian AE, Landsman D, Lockhart DJ, Davis RW (1998) A genome-wide transcriptional analysis of the mitotic cell cycle. Mol Cell 2:65–73
Cho RJ, Huang M, Campbell MJ, Dong H, Steinmetz L, Sapinoso L, Hampton G, Elledge SJ, Davis RW, Lockhart DJ (2001) Transcriptional regulation and function during the human cell cycle. Nat Genet 27:48–54. doi:10.1038/83751
Coldwell MJ, Cowan JL, Vlasak M, Mead A, Willett M, Perry LS, Morley SJ (2013) Phosphorylation of eIF4GII and 4E-BP1 in response to nocodazole treatment: a reappraisal of translation initiation during mitosis. Cell Cycle (Georgetown, Tex) 12:3615–3628. doi:10.4161/cc.26588
Csardi G, Franks A, Choi DS, Airoldi EM, Drummond DA (2015) Accounting for experimental noise reveals that mRNA levels, amplified by post-transcriptional processes, largely determine steady-state protein levels in yeast. PLoS Genet 11:e1005206. doi:10.1371/journal.pgen.1005206
de Lichtenberg U, Jensen LJ, Brunak S, Bork P (2005) Dynamic complex formation during the yeast cell cycle. Science 307:724–727. doi:10.1126/science.1105103
Denais CM, Gilbert RM, Isermann P, McGregor AL, te Lindert M, Weigelin B, Davidson PM, Friedl P, Wolf K, Lammerding J (2016) Nuclear envelope rupture and repair during cancer cell migration. Science 352:353–358. doi:10.1126/science.aad7297
Di Fiore B, Pines J (2008) Defining the role of Emi1 in the DNA replication-segregation cycle. Chromosoma 117:333–338. doi:10.1007/s00412-008-0152-x
Di Talia S, Skotheim JM, Bean JM, Siggia ED, Cross FR (2007) The effects of molecular noise and size control on variability in the budding yeast cell cycle. Nature 448:947–951. doi:10.1038/nature06072
Dobrikov MI, Shveygert M, Brown MC, Gromeier M (2014) Mitotic phosphorylation of eukaryotic initiation factor 4G1 (eIF4G1) at Ser1232 by Cdk1:cyclin B inhibits eIF4A helicase complex binding with RNA. Mol Cell Biol 34:439–451. doi:10.1128/mcb.01046-13
Elserafy M, Saric M, Neuner A, Lin TC, Zhang W, Seybold C, Sivashanmugam L, Schiebel E (2014) Molecular mechanisms that restrict yeast centrosome duplication to one event per cell cycle. Curr Biol CB 24:1456–1466. doi:10.1016/j.cub.2014.05.032
Evans T, Rosenthal ET, Youngblom J, Distel D, Hunt T (1983) Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell 33:389–396
Gordon CN, Elliott SC (1977) Fractionation of Saccharomyces cerevisiae cell populations by centrifugal elutriation. J Bacteriol 129:97–100
Ingolia NT, Ghaemmaghami S, Newman JR, Weissman JS (2009) Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324:218–223. doi:10.1126/science.1168978
Jaspersen SL, Winey M (2004) The budding yeast spindle pole body: structure, duplication, and function. Annu Rev Cell Dev Biol 20:1–28. doi:10.1146/annurev.cellbio.20.022003.114106
Kuwada NJ, Traxler B, Wiggins PA (2015) High-throughput cell-cycle imaging opens new doors for discovery. Curr Genet 61:513–516. doi:10.1007/s00294-015-0493-y
Larsson O, Sonenberg N, Nadon R (2011) Anota: analysis of differential translation in genome-wide studies. Bioinformatics 27:1440–1441. doi:10.1093/bioinformatics/btr146
Li JJ, Biggin MD (2015) Gene expression. Statistics requantitates the central dogma. Science 347:1066–1067. doi:10.1126/science.aaa8332
Li JJ, Bickel PJ, Biggin MD (2014) System wide analyses have underestimated protein abundances and the importance of transcription in mammals. Peer J 2:e270. doi:10.7717/peerj.270
Ly T, Ahmad Y, Shlien A, Soroka D, Mills A, Emanuele MJ, Stratton MR, Lamond AI (2014) A proteomic chronology of gene expression through the cell cycle in human myeloid leukemia cells. Elife 3:e01630. doi:10.7554/eLife.01630
Ly T, Endo A, Lamond AI (2015) Proteomic analysis of the response to cell cycle arrests in human myeloid leukemia cells. Elife 4:e04534. doi:10.7554/eLife.04534
Mitchison JM (1971a) Cell growth and protein synthesis the biology of the cell cycle. Cambridge University Press, Cambridge, p 129
Mitchison JM (1971b) Synchronous cultures the biology of the cell cycle. Cambridge University Press, Cambridge, pp 25–57
Olshen AB, Hsieh AC, Stumpf CR, Olshen RA, Ruggero D, Taylor BS (2013) Assessing gene-level translational control from ribosome profiling. Bioinformatics 29:2995–3002. doi:10.1093/bioinformatics/btt533
Polymenis M, Aramayo R (2015) Translate to divide: control of the cell cycle by protein synthesis. Microb Cell 2:94–104. doi:10.15698/mic2015.04.198
Raab M, Gentili M, de Belly H, Thiam HR, Vargas P, Jimenez AJ, Lautenschlaeger F, Voituriez R, Lennon-Dumenil AM, Manel N, Piel M (2016) ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death. Science 352:359–362. doi:10.1126/science.aad7611
Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (2005) Phosphorylation and regulation of Akt/PKB by the rictor–mTOR complex. Science 307:1098–1101. doi:10.1126/science.1106148
Sole C, Nadal-Ribelles M, de Nadal E, Posas F (2015) A novel role for lncRNAs in cell cycle control during stress adaptation. Curr Genet 61:299–308. doi:10.1007/s00294-014-0453-y
Spellman PT, Sherlock G, Zhang MQ, Iyer VR, Anders K, Eisen MB, Brown PO, Botstein D, Futcher B (1998) Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 9:3273–3297
Stumpf CR, Moreno MV, Olshen AB, Taylor BS, Ruggero D (2013) The translational landscape of the mammalian cell cycle. Mol Cell 52:574–582. doi:10.1016/j.molcel.2013.09.018
Tanenbaum ME, Stern-Ginossar N, Weissman JS, Vale RD (2015) Regulation of mRNA translation during mitosis. Elife 4:e07957. doi:10.7554/eLife.07957
Ungricht R, Kutay U (2017) Mechanisms and functions of nuclear envelope remodelling. Nat Rev Mol Cell Biol 18:229–245. doi:10.1038/nrm.2016.153
Walters AD, May CK, Dauster ES, Cinquin BP, Smith EA, Robellet X, D’Amours D, Larabell CA, Cohen-Fix O (2014) The yeast polo kinase Cdc5 regulates the shape of the mitotic nucleus. Curr Biol CB 24:2861–2867. doi:10.1016/j.cub.2014.10.029
Whitfield ML, Sherlock G, Saldanha AJ, Murray JI, Ball CA, Alexander KE, Matese JC, Perou CM, Hurt MM, Brown PO, Botstein D (2002) Identification of genes periodically expressed in the human cell cycle and their expression in tumors. Mol Biol Cell 13:1977–2000. doi:10.1091/mbc.02-02-0030
Acknowledgements
Funding was provided by National Institute of General Medical Sciences (Grant No. R01GM123139).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Communicated by M. Kupiec.
Rights and permissions
About this article
Cite this article
Aramayo, R., Polymenis, M. Ribosome profiling the cell cycle: lessons and challenges. Curr Genet 63, 959–964 (2017). https://doi.org/10.1007/s00294-017-0698-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00294-017-0698-3