Abstract
To ensure proper chromosome segregation during cell division, the centromere in many organisms is transcribed to produce a low level of long non-coding RNA to regulate the activity of the kinetochore. In the budding yeast point centromere, our recent work has shown that the level of centromeric RNAs (cenRNAs) is tightly regulated and repressed by the kinetochore protein Cbf1 and histone H2A variant H2A.ZHtz1, and de-repressed during S phase of the cell cycle. Too little or too much cenRNAs will disrupt centromere activity. Here, we discuss the current advance in the understanding of the action and regulation of cenRNAs at the point centromere of Saccharomyces cerevisiae. We further show that budding yeast cenRNAs are cryptic unstable transcripts (CUTs) that can be degraded by the nuclear RNA decay pathway. CenRNA provides an example that even CUTs, when present at the right time with the right level, can serve important cellular functions.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Albert I, Mavrich TN, Tomsho LP, Qi J, Zanton SJ, Schuster SC, Pugh BF (2007) Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome. Nature 446:572–576. https://doi.org/10.1038/nature05632
Baker RE, Fitzgerald-Hayes M, O’Brien TC (1989) Purification of the yeast centromere binding protein CP1 and a mutational analysis of its binding site. J Biol Chem 264:10843–10850
Bergmann JH, Jakubsche JN, Martins NM, Kagansky A, Nakano M, Kimura H, Kelly DA, Turner BM, Masumoto H, Larionov V, Earnshaw WC (2012) Epigenetic engineering: histone H3K9 acetylation is compatible with kinetochore structure and function. J Cell Sci 125:411–421. https://doi.org/10.1242/jcs.090639
Berretta J, Pinskaya M, Morillon A (2008) A cryptic unstable transcript mediates transcriptional trans-silencing of the Ty1 retrotransposon in S. cerevisiae. Genes Dev 22:615–626. https://doi.org/10.1101/gad.458008
Blower MD (2016) Centromeric transcription regulates aurora-B localization and activation. Cell Rep 15:1624–1633. https://doi.org/10.1016/j.celrep.2016.04.054
Bobkov GOM, Gilbert N, Heun P (2018) Centromere transcription allows CENP-A to transit from chromatin association to stable incorporation. J Cell Biol 217:1957–1972. https://doi.org/10.1083/jcb.201611087
Bram RJ, Kornberg RD (1987) Isolation of a Saccharomyces cerevisiae centromere DNA-binding protein, its human homolog, and its possible role as a transcription factor. Mol Cell Biol 7:403–409
Buehl CJ, Kuo MH (2018) Critical roles of Shugoshin and histones as tension sensors during mitosis. Curr Genet 64:1215–1219. https://doi.org/10.1007/s00294-018-0846-4
Cai M, Davis RW (1990) Yeast centromere binding protein CBF1, of the helix-loop-helix protein family, is required for chromosome stability and methionine prototrophy. Cell 61:437–446
Camblong J, Iglesias N, Fickentscher C, Dieppois G, Stutz F (2007) Antisense RNA stabilization induces transcriptional gene silencing via histone deacetylation in S. cerevisiae. Cell 131:706–717. https://doi.org/10.1016/j.cell.2007.09.014
Candelli T, Challal D, Briand JB, Boulay J, Porrua O, Colin J, Libri D (2018) High-resolution transcription maps reveal the widespread impact of roadblock termination in yeast. EMBO J. https://doi.org/10.15252/embj.201797490
Catania S, Pidoux AL, Allshire RC (2015) Sequence features and transcriptional stalling within centromere DNA promote establishment of CENP-A chromatin. PLoS Genet 11:e1004986. https://doi.org/10.1371/journal.pgen.1004986
Chan FL, Marshall OJ, Saffery R, Kim BW, Earle E, Choo KH, Wong LH (2012) Active transcription and essential role of RNA polymerase II at the centromere during mitosis. Proc Natl Acad Sci USA 109:1979–1984. https://doi.org/10.1073/pnas.1108705109
Chen CC, Bowers S, Lipinszki Z, Palladino J, Trusiak S, Bettini E, Rosin L, Przewloka MR, Glover DM, O’Neill RJ, Mellone BG (2015) Establishment of centromeric chromatin by the CENP-A assembly factor CAL1 requires FACT-mediated transcription. Dev Cell 34:73–84. https://doi.org/10.1016/j.devcel.2015.05.012
Choi ES, Stralfors A, Castillo AG, Durand-Dubief M, Ekwall K, Allshire RC (2011) Identification of noncoding transcripts from within CENP-A chromatin at fission yeast centromeres. J Biol Chem 286:23600–23607. https://doi.org/10.1074/jbc.M111.228510
Dhatchinamoorthy K, Mattingly M, Gerton JL (2018) Regulation of kinetochore configuration during mitosis. Curr Genet 64:1197–1203. https://doi.org/10.1007/s00294-018-0841-9
Du Y, Topp CN, Dawe RK (2010) DNA binding of centromere protein C (CENPC) is stabilized by single-stranded RNA. PLoS Genet 6:e1000835. https://doi.org/10.1371/journal.pgen.1000835
Ferri F, Bouzinba-Segard H, Velasco G, Hube F, Francastel C (2009) Non-coding murine centromeric transcripts associate with and potentiate Aurora B kinase. Nucleic Acids Res 37:5071–5080. https://doi.org/10.1093/nar/gkp529
Furuyama S, Biggins S (2007) Centromere identity is specified by a single centromeric nucleosome in budding yeast. Proc Natl Acad Sci USA 104:14706–14711. https://doi.org/10.1073/pnas.0706985104
Greaves IK, Rangasamy D, Ridgway P, Tremethick DJ (2007) H2A.Z contributes to the unique 3D structure of the centromere. Proc Natl Acad Sci USA 104:525–530. https://doi.org/10.1073/pnas.0607870104
Hill A, Bloom K (1987) Genetic manipulation of centromere function. Mol Cell Biol 7:2397–2405
Hou H, Wang Y, Kallgren SP, Thompson J, Yates JR 3rd, Jia S (2010) Histone variant H2A.Z regulates centromere silencing and chromosome segregation in fission yeast. J Biol Chem 285:1909–1918. https://doi.org/10.1074/jbc.M109.058487
Houseley J, Kotovic K, El Hage A, Tollervey D (2007) Trf4 targets ncRNAs from telomeric and rDNA spacer regions and functions in rDNA copy number control. EMBO J 26:4996–5006. https://doi.org/10.1038/sj.emboj.7601921
Ideue T, Cho Y, Nishimura K, Tani T (2014) Involvement of satellite I noncoding RNA in regulation of chromosome segregation. Genes Cells 19:528–538. https://doi.org/10.1111/gtc.12149
Jin QW, Fuchs J, Loidl J (2000) Centromere clustering is a major determinant of yeast interphase nuclear organization. J Cell Sci 113(Pt 11):1903–1912
Kamakaka RT, Biggins S (2005) Histone variants: deviants? Genes Dev 19:295–310. https://doi.org/10.1101/gad.1272805
Kitamura E, Tanaka K, Kitamura Y, Tanaka TU (2007) Kinetochore microtubule interaction during S phase in Saccharomyces cerevisiae. Genes Dev 21:3319–3330. https://doi.org/10.1101/gad.449407
Kolaczkowski M, Kolaczkowska A, Gaigg B, Schneiter R, Moye-Rowley WS (2004) Differential regulation of ceramide synthase components LAC1 and LAG1 in Saccharomyces cerevisiae. Eukaryot Cell 3:880–892. https://doi.org/10.1128/EC.3.4.880-892.2004
Kulaeva OI, Gaykalova DA, Studitsky VM (2007) Transcription through chromatin by RNA polymerase II: histone displacement and exchange. Mutat Res 618:116–129. https://doi.org/10.1016/j.mrfmmm.2006.05.040
LaCava J, Houseley J, Saveanu C, Petfalski E, Thompson E, Jacquier A, Tollervey D (2005) RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 121:713–724. https://doi.org/10.1016/j.cell.2005.04.029
Lechner J, Carbon J (1991) A 240 kd multisubunit protein complex, CBF3, is a major component of the budding yeast centromere. Cell 64:717–725
Ling YH, Yuen KWY (2019) Point centromere activity requires an optimal level of centromeric noncoding RNA. Proc Natl Acad Sci USA 116:6270–6279. https://doi.org/10.1073/pnas.1821384116
McNulty SM, Sullivan LL, Sullivan BA (2017) Human centromeres produce chromosome-specific and array-specific alpha satellite transcripts that are complexed with CENP-A and CENP-C. Dev Cell 42(226–240):e226. https://doi.org/10.1016/j.devcel.2017.07.001
Mellor J, Jiang W, Funk M, Rathjen J, Barnes CA, Hinz T, Hegemann JH, Philippsen P (1990) CPF1, a yeast protein which functions in centromeres and promoters. EMBO J 9:4017–4026
Meneghini MD, Wu M, Madhani HD (2003) Conserved histone variant H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin. Cell 112:725–736
Nakagawa T, Okita AK (2019) Transcriptional silencing of centromere repeats by heterochromatin safeguards chromosome integrity. Curr Genet. https://doi.org/10.1007/s00294-019-00975-x
Neil H, Malabat C, d’Aubenton-Carafa Y, Xu Z, Steinmetz LM, Jacquier A (2009) Widespread bidirectional promoters are the major source of cryptic transcripts in yeast. Nature 457:1038–1042. https://doi.org/10.1038/nature07747
Ohkuni K, Kitagawa K (2011) Endogenous transcription at the centromere facilitates centromere activity in budding yeast. Curr Biol 21:1695–1703. https://doi.org/10.1016/j.cub.2011.08.056
Pezer Z, Ugarkovic D (2008) RNA Pol II promotes transcription of centromeric satellite DNA in beetles. PLoS One 3:e1594. https://doi.org/10.1371/journal.pone.0001594
Pluta AF, Mackay AM, Ainsztein AM, Goldberg IG, Earnshaw WC (1995) The centromere: hub of chromosomal activities. Science 270:1591–1594
Quenet D, Dalal Y (2014) A long non-coding RNA is required for targeting centromeric protein A to the human centromere. Elife 3:e03254. https://doi.org/10.7554/eLife.03254
Rosic S, Kohler F, Erhardt S (2014) Repetitive centromeric satellite RNA is essential for kinetochore formation and cell division. J Cell Biol 207:335–349. https://doi.org/10.1083/jcb.201404097
Stephens AD, Snider CE, Haase J, Haggerty RA, Vasquez PA, Forest MG, Bloom K (2013) Individual pericentromeres display coordinated motion and stretching in the yeast spindle. J Cell Biol 203:407–416. https://doi.org/10.1083/jcb.201307104
Talbert PB, Henikoff S (2018) Transcribing centromeres: noncoding RNAs and kinetochore assembly. Trends Genet 34:587–599. https://doi.org/10.1016/j.tig.2018.05.001
Thomas D, Jacquemin I, Surdin-Kerjan Y (1992) MET4, a leucine zipper protein, and centromere-binding factor 1 are both required for transcriptional activation of sulfur metabolism in Saccharomyces cerevisiae. Mol Cell Biol 12:1719–1727
Topp CN, Zhong CX, Dawe RK (2004) Centromere-encoded RNAs are integral components of the maize kinetochore. Proc Natl Acad Sci USA 101:15986–15991. https://doi.org/10.1073/pnas.0407154101
Vanacova S, Wolf J, Martin G, Blank D, Dettwiler S, Friedlein A, Langen H, Keith G, Keller W (2005) A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol 3:e189. https://doi.org/10.1371/journal.pbio.0030189
Westhorpe FG, Straight AF (2014) The centromere: epigenetic control of chromosome segregation during mitosis. Cold Spring Harb Perspect Biol 7:a015818. https://doi.org/10.1101/cshperspect.a015818
Wong LH, Brettingham-Moore KH, Chan L, Quach JM, Anderson MA, Northrop EL, Hannan R, Saffery R, Shaw ML, Williams E, Choo KH (2007) Centromere RNA is a key component for the assembly of nucleoproteins at the nucleolus and centromere. Genome Res 17:1146–1160. https://doi.org/10.1101/gr.6022807
Wyers F, Rougemaille M, Badis G, Rousselle JC, Dufour ME, Boulay J, Regnault B, Devaux F, Namane A, Seraphin B, Libri D, Jacquier A (2005) Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 121:725–737. https://doi.org/10.1016/j.cell.2005.04.030
Xu Z, Wei W, Gagneur J, Perocchi F, Clauder-Munster S, Camblong J, Guffanti E, Stutz F, Huber W, Steinmetz LM (2009) Bidirectional promoters generate pervasive transcription in yeast. Nature 457:1033–1037. https://doi.org/10.1038/nature07728
Zhang H, Roberts DN, Cairns BR (2005) Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss. Cell 123:219–231. https://doi.org/10.1016/j.cell.2005.08.036
Acknowledgements
This research was funded by the Hong Kong Research Grants Council General Research Fund (Project Number: 17113418) and Collaborative Research Fund (Project Number: C7058-18GF), and the University of Hong Kong Seed Funds for Basic Research (Project Numbers: 201311159169 and 201509159021).
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by M. Kupiec.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ling, Y.H., Yuen, K.W.Y. Centromeric non-coding RNA as a hidden epigenetic factor of the point centromere. Curr Genet 65, 1165–1171 (2019). https://doi.org/10.1007/s00294-019-00988-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00294-019-00988-6