The oocyte-to-embryo transition (OET) transforms a differentiated gamete into pluripotent blastomeres. The accompanying maternal-zygotic RNA exchange involves remodeling of the long non-coding RNA (lncRNA) pool. Here, we used next generation sequencing and de novo transcript assembly to define the core population of 1,600 lncRNAs expressed during the OET (lncRNAs). Relative to mRNAs, OET lncRNAs were less expressed and had shorter transcripts, mainly due to fewer exons and shorter 5' terminal exons. Approximately half of OET lncRNA promoters originated in retrotransposons suggesting their recent emergence. Except for a small group of ubiquitous lncRNAs, maternal and zygotic lncRNAs formed two distinct populations. The bulk of maternal lncRNAs was degraded before the zygotic genome activation. Interestingly, maternal lncRNAs seemed to undergo cytoplasmic polyadenylation observed for dormant mRNAs. We also identified lncRNAs giving rise to trans-acting short interfering RNAs, which represent a novel lncRNA category. Altogether, we defined the core OET lncRNA transcriptome and characterized its remodeling during early development. Our results are consistent with the notion that rapidly evolving lncRNAs constitute signatures of cells-of-origin while a minority plays an active role in control of gene expression across OET. Our data presented here provide an excellent source for further OET lncRNA studies.

Bioinformatics Group Division of Molecular Biology Department of Biology Faculty of Science University of Zagreb Horvatovac 102a Zagreb Croatia

Department of Computational Biology and Medical Sciences Graduate School of Frontier Sciences The University of Tokyo Kashiwa Japan

Department of Integrated Biosciences Graduate School of Frontier Sciences The University of Tokyo Kashiwa Japan

Institute of Molecular Genetics Academy of Sciences of the Czech Republic Videnska 1083 142 20 Prague 4 Czech Republic

Erratum In

DNA Res. 2017 Apr 1;24(2):219-220. doi: 10.1093/dnares/dsx008. PubMed

See more in PubMed

Svoboda P., Franke V., Schultz R.M.. 2015, Sculpting the transcriptome during the oocyte-to-embryo transition in mouse. Curr. Top. Dev. Biol., 113, 305–49. PubMed

Marques A.C., Ponting C.P.. 2014, Intergenic lncRNAs and the evolution of gene expression. Curr. Opin. Genet. Dev., 27, 48–53. PubMed

Guttman M., Rinn J.L.. 2012, Modular regulatory principles of large non-coding RNAs. Nature, 482, 339–46. PubMed PMC

Mercer T.R., Mattick J.S.. 2013, Structure and function of long noncoding RNAs in epigenetic regulation. Nat. Struct. Mol. Biol., 20, 300–7. PubMed

Ulitsky I., Bartel D.P.. 2013, lincRNAs: genomics, evolution, and mechanisms. Cell, 154, 26–46. PubMed PMC

Kutter C., Watt S., Stefflova K., et al. 2012, Rapid turnover of long noncoding RNAs and the evolution of gene expression. PLoS Genet., 8, e1002841. PubMed PMC

Ng S.Y., Stanton L.W.. 2013, Long non-coding RNAs in stem cell pluripotency. Wiley Interdiscip. Rev. RNA, 4, 121–8. PubMed

Yan L., Yang M., Guo H., et al. 2013, Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells. Nat. Struct. Mol. Biol., 20, 1131–9. PubMed

Zhang K., Huang K., Luo Y., Li S.. 2014, Identification and functional analysis of long non-coding RNAs in mouse cleavage stage embryonic development based on single cell transcriptome data. BMC Genomics, 15, 845. PubMed PMC

Hamazaki N., Uesaka M., Nakashima K., Agata K., Imamura T.. 2015, Gene activation-associated long noncoding RNAs function in mouse preimplantation development. Development, 142, 910–20. PubMed PMC

Veselovska L., Smallwood S. A., Saadeh H., et al. 2015, Deep sequencing and de novo assembly of the mouse oocyte transcriptome define the contribution of transcription to the DNA methylation landscape. Genome Biol., 16, 209. PubMed PMC

Abe K., Yamamoto R., Franke V., et al. 2015, The first murine zygotic transcription is promiscuous and uncoupled from splicing and 3' processing. EMBO J., 34, 1523–37. PubMed PMC

Nagy A. 2003, Manipulating the Mouse Embryo: A Laboratory Manual. Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY.

Flemr M., Malik R., Franke V., et al. 2013, A retrotransposon-driven dicer isoform directs endogenous small interfering RNA production in mouse oocytes. Cell, 155, 807–16. PubMed

Cong L., Ran F.A., Cox D., et al. Multiplex genome engineering using CRISPR/Cas systems. Science, 339, 819–23. PubMed PMC

Chen B., Gilbert L. A., Cimini B. A., et al. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell, 155, 1479–91. PubMed PMC

Park S.J., Komata M., Inoue F., et al. 2013, Inferring the choreography of parental genomes during fertilization from ultralarge-scale whole-transcriptome analysis. Genes Dev., 27, 2736–48. PubMed PMC

Xue Z., Huang K., Cai C., et al. 2013, Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing. Nature, 500, 593–7. PubMed PMC

Guttman M., Garber M., Levin J. Z., et al. 2010, Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs. Nat. Biotechnol., 28, 503–10. PubMed PMC

Wang L., Park H.J., Dasari S., Wang S., Kocher J.P., Li W.. 2013, CPAT: coding-potential assessment tool using an alignment-free logistic regression model. Nucleic Acids Res., 41, e74. PubMed PMC

Tarailo-Graovac M., Chen N.. 2009, Using RepeatMasker to identify repetitive elements in genomic sequences. Curr. Protoc. Bioinformatics, Chapter 4, Unit 4 10. PubMed

Stein P., Rozhkov N.V., Li F., et al. 2015, Essential Role for endogenous siRNAs during meiosis in mouse oocytes. PLoS Genet., 11, e1005013. PubMed PMC

Tam O.H., Aravin A.A., Stein P., et al. 2008, Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature, 453, 534–8. PubMed PMC

Flemr M., Ma J., Schultz R. M., Svoboda P.. 2010, P-body loss is concomitant with formation of a messenger RNA storage domain in mouse oocytes. Biol. Reprod, 82, 1008–17. PubMed PMC

Guttman M., Amit I., Garber M., et al. 2009, Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature, 458, 223–7. PubMed PMC

Kelley D., Rinn J.. 2012, Transposable elements reveal a stem cell-specific class of long noncoding RNAs. Genome Biol, 13, R107. PubMed PMC

Piko L., Clegg K.B.. 1982, Quantitative changes in total Rna, total Poly(a), and ribosomes in early mouse embryos. Dev. Biol., 89, 362–78. PubMed

Cabili M.N., Trapnell C., Goff L., et al. 2011, Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev., 25, 1915–27. PubMed PMC

Derrien T., Johnson R., Bussotti G., et al. 2012, The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res., 22, 1775–89. PubMed PMC

Ulitsky I., Shkumatava A., Jan C. H., Sive H., Bartel D.P.. 2011, Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell, 147, 1537–50. PubMed PMC

Smallwood S.A., Tomizawa S., Krueger F., et al. 2011, Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nat. Genet., 43, 811–4. PubMed PMC

Marzluff W.F., Gongidi P., Woods K.R., Jin J., Maltais L.J.. 2002, The human and mouse replication-dependent histone genes. Genomics, 80, 487–98. PubMed

Richter J.D., Lasko P.. 2011, Translational control in oocyte development. Cold Spring Harb. Perspect. Biol., 3, a002758. PubMed PMC

Gebauer F., Richter J.D.. 1997, Synthesis and function of Mos: the control switch of vertebrate oocyte meiosis. Bioessays, 19, 23–8. PubMed

Huarte J., Belin D., Vassalli A., Strickland S., Vassalli J.D.. 1987, Meiotic maturation of mouse oocytes triggers the translation and polyadenylation of dormant tissue-type plasminogen activator mRNA. Genes Dev., 1, 1201–11. PubMed

de Vantery C., Stutz A., Vassalli J.D., Schorderet-Slatkine S.. 1997, Acquisition of meiotic competence in growing mouse oocytes is controlled at both translational and posttranslational levels. Dev. Biol., 187, 43–54. PubMed

Murai S., Stein P., Buffone M.G., Yamashita S., Schultz R.M.. 2010, Recruitment of Orc6l, a dormant maternal mRNA in mouse oocytes, is essential for DNA replication in 1-cell embryos. Dev. Biol., 341, 205–12. PubMed PMC

Ma J., Flemr M., Strnad H., Svoboda P., Schultz R.M.. 2013, Maternally recruited DCP1A and DCP2 contribute to messenger RNA degradation during oocyte maturation and genome activation in mouse. Biol. Reprod., 88, 11. PubMed PMC

Charlesworth A., Cox L.L., MacNicol A.M.. 2004, Cytoplasmic polyadenylation element (CPE)- and CPE-binding protein (CPEB)-independent mechanisms regulate early class maternal mRNA translational activation in Xenopus oocytes. J. Biol. Chem., 279, 17650–9. PubMed PMC

Alizadeh Z., Kageyama S., Aoki F.. 2005, Degradation of maternal mRNA in mouse embryos: selective degradation of specific mRNAs after fertilization. Mol. Reprod. Dev., 72, 281–90. PubMed

Sakurai T., Sato M., Kimura M.. 2005, Diverse patterns of poly(A) tail elongation and shortening of murine maternal mRNAs from fully grown oocyte to 2-cell embryo stages. Biochem. Biophys. Res. Commun., 336, 1181–9. PubMed

Carlevaro-Fita J., Rahim A., Guigo R., Vardy L.A., Johnson R.. 2016, Cytoplasmic long noncoding RNAs are frequently bound to and degraded at ribosomes in human cells. RNA, 22, 867–82. PubMed PMC

Ruiz-Orera J., Messeguer X., Subirana J.A., Alba M.M.. 2014, Long non-coding RNAs as a source of new peptides. Elife, 3, e03523. PubMed PMC

Yue F., Cheng Y., Breschi A., et al. 2014, A comparative encyclopedia of DNA elements in the mouse genome. Nature, 515, 355–64. PubMed PMC

Gutschner T., Hammerle M., Diederichs S.. 2013, MALAT1 – a paradigm for long noncoding RNA function in cancer. J. Mol. Med. (Berl), 91, 791–801. PubMed

Eissmann M., Gutschner T., Hammerle M., et al. 2012, Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and development. RNA Biol., 9, 1076–87. PubMed PMC

Zhang B., Arun G., Mao Y. S., et al. 2012, The lncRNA Malat1 is dispensable for mouse development but its transcription plays a cis-regulatory role in the adult. Cell Rep., 2, 111–23. PubMed PMC

Nakagawa S., Ip J. Y., Shioi G., et al. 2012, Malat1 is not an essential component of nuclear speckles in mice. RNA, 18, 1487–99. PubMed PMC

Watanabe T., Totoki Y., Toyoda A., et al. 2008, Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature, 453, 539–43. PubMed

Garcia-Lopez J., Alonso L., Cardenas D.B., et al. 2015, Diversity and functional convergence of small noncoding RNAs in male germ cell differentiation and fertilization. RNA, 21, 946–62. PubMed PMC

Garcia-Lopez J., Hourcade Jde D., Alonso L., Cardenas D.B., del Mazo J.. 2014, Global characterization and target identification of piRNAs and endo-siRNAs in mouse gametes and zygotes. Biochim. Biophys. Acta, 1839, 463–75. PubMed

Svoboda P., Flemr M.. 2010, The role of miRNAs and endogenous siRNAs in maternal-to-zygotic reprogramming and the establishment of pluripotency. EMBO Rep., 11, 590–7. PubMed PMC

Ma J., Flemr M., Stein P., et al. 2010, MicroRNA activity is suppressed in mouse oocytes. Curr. Biol., 20, 265–70. PubMed PMC

Watanabe T., Cheng E.C., Zhong M., Lin H.. 2015, Retrotransposons and pseudogenes regulate mRNAs and lncRNAs via the piRNA pathway in the germline. Genome Res., 25, 368–80. PubMed PMC

Nejepinska J., Malik R., Filkowski J., Flemr M., Filipowicz W., Svoboda P.. 2012, dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cells. Nucleic Acids Res., 40, 399–413. PubMed PMC

Kumar S., Hedges S.B.. 1998, A molecular timescale for vertebrate evolution. Nature, 392, 917–20. PubMed

Functional canonical RNAi in mice expressing a truncated Dicer isoform and long dsRNA

De novo emergence, existence, and demise of a protein-coding gene in murids

ncRNA BC1 influences translation in the oocyte

MicroRNA dilution during oocyte growth disables the microRNA pathway in mammalian oocytes

The most abundant maternal lncRNA Sirena1 acts post-transcriptionally and impacts mitochondrial distribution

Identifying the Translatome of Mouse NEBD-Stage Oocytes via SSP-Profiling; A Novel Polysome Fractionation Method

Role of Cnot6l in maternal mRNA turnover