Ribosome profiling reveals the what, when, where and how of protein synthesis (original) (raw)

• McCann, K. L. & Baserga, S. J. Mysterious ribosomopathies. Science 341, 849–850 (2013).
  CAS PubMed PubMed Central Google Scholar
• Cleary, J. D. & Ranum, L. P. W. Repeat-associated non-ATG (RAN) translation in neurological disease. Hum. Mol. Genet. 22, R45–R51 (2013).
  CAS PubMed PubMed Central Google Scholar
• Ellis, S. R. Nucleolar stress in Diamond Blackfan anemia pathophysiology. Biochim. Biophys. Acta 1842, 765–768 (2014).
  CAS PubMed Google Scholar
• Trainor, P. A. & Merrill, A. E. Ribosome biogenesis in skeletal development and the pathogenesis of skeletal disorders. Biochim. Biophys. Acta 1842, 769–778 (2014).
  CAS PubMed Google Scholar
• Bolze, A. et al. Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia. Science 340, 976–978 (2013).
  CAS PubMed PubMed Central Google Scholar
• Kondrashov, N. et al. Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning. Cell 145, 383–397 (2011).
  CAS PubMed PubMed Central Google Scholar
• Ingolia, N. T., Ghaemmaghami, S., Newman, J. R. S. & Weissman, J. S. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324, 218–223 (2009). This work defines the ribosome profiling method and details its specificity, precision and utility.
  Article CAS PubMed PubMed Central Google Scholar
• Wolin, S. L. & Walter, P. Ribosome pausing and stacking during translation of a eukaryotic mRNA. EMBO J. 7, 3559–3569 (1988).
  CAS PubMed PubMed Central Google Scholar
• Steitz, J. A. Polypeptide chain initiation: nucleotide sequences of the three ribosomal binding sites in bacteriophage R17 RNA. Nature 224, 957–964 (1969).
  CAS PubMed Google Scholar
• Ingolia, N. T., Lareau, L. F. & Weissman, J. S. Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell 147, 789–802 (2011).
  CAS PubMed PubMed Central Google Scholar
• Stern-Ginossar, N. et al. Decoding human cytomegalovirus. Science 338, 1088–1093 (2012).
  CAS PubMed Google Scholar
• Brar, G. A. et al. High-resolution view of the yeast meiotic program revealed by ribosome profiling. Science 335, 552–557 (2012). References 11 and 12 describe the application of ribosome profiling to physiological dynamic cellular processes, the HCMV infection cycle in human cells and meiosis in budding yeast, respectively. In these disparate systems, both studies identified many new examples of translational control, uORF translation and the translation of many sORFs and alternative ORFs in genomic regions that were thought to be non-coding.
  CAS PubMed Google Scholar
• Bazzini, A. A. et al. Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation. EMBO J. 33, 981–993 (2014).
  CAS PubMed PubMed Central Google Scholar
• Pauli, A. et al. Toddler: an embryonic signal that promotes cell movement via Apelin receptors. Science 343, 1248636 (2014).
  PubMed PubMed Central Google Scholar
• Dunn, J. G., Foo, C. K., Belletier, N. G., Gavis, E. R. & Weissman, J. S. Ribosome profiling reveals pervasive and regulated stop codon readthrough in Drosophila melanogaster. eLife 2, e01179 (2013).
  PubMed PubMed Central Google Scholar
• Aspden, J. L. et al. Extensive translation of small open reading frames revealed by Poly-Ribo-Seq. eLife 3, e03528 (2014).
  PubMed PubMed Central Google Scholar
• Smith, J. E. et al. Translation of small open reading frames within unannotated RNA transcripts in Saccharomyces cerevisiae. Cell Rep. 7, 1858–1866 (2014).
  CAS PubMed PubMed Central Google Scholar
• Lee, S. et al. Global mapping of translation initiation sites in mammalian cells at single-nucleotide resolution. Proc. Natl Acad. Sci. USA 109, E2424–E2432 (2012).
  CAS PubMed PubMed Central Google Scholar
• Andreev, D. E. et al. Translation of 5′ leaders is pervasive in genes resistant to eIF2 repression. eLife 4, e03971 (2014).
  Google Scholar
• Van Dijk, E. L., Auger, H., Jaszczyszyn, Y. & Thermes, C. Ten years of next-generation sequencing technology. Trends Genet. 30, 418–426 (2014).
  CAS PubMed Google Scholar
• Ingolia, N. T., Brar, G. A., Rouskin, S., McGeachy, A. M. & Weissman, J. S. The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragments. Nat. Protoc. 7, 1534–1550 (2012).
  CAS PubMed PubMed Central Google Scholar
• Kuersten, S., Radek, A., Vogel, C. & Penalva, L. O. Translation regulation gets its 'omics' moment. Wiley Interdiscip. Rev. RNA 4, 617–630 (2013).
  CAS PubMed PubMed Central Google Scholar
• Oh, E. et al. Selective ribosome profiling reveals the cotranslational chaperone action of trigger factor in vivo. Cell 147, 1295–1308 (2011).
  CAS PubMed PubMed Central Google Scholar
• Arias, C. et al. KSHV 2.0: a comprehensive annotation of the Kaposi's sarcoma-associated herpesvirus genome using next-generation sequencing reveals novel genomic and functional features. PLoS Pathog. 10, e1003847 (2014).
  PubMed PubMed Central Google Scholar
• Stadler, M. & Fire, A. Wobble base-pairing slows in vivo translation elongation in metazoans. RNA 17, 2063–2073 (2011).
  CAS PubMed PubMed Central Google Scholar
• Bazzini, A. A., Lee, M. T. & Giraldez, A. J. Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish. Science 336, 233–237 (2012).
  CAS PubMed PubMed Central Google Scholar
• Juntawong, P., Girke, T., Bazin, J. & Bailey-Serres, J. Translational dynamics revealed by genome-wide profiling of ribosome footprints in Arabidopsis. Proc. Natl Acad. Sci. USA 111, E203–E212 (2014).
  CAS PubMed Google Scholar
• Jensen, B. C. et al. Extensive stage-regulation of translation revealed by ribosome profiling of Trypanosoma brucei. BMC Genomics 15, 911 (2014).
  PubMed PubMed Central Google Scholar
• Caro, F., Ahyong, V., Betegon, M. & DeRisi, J. L. Genome-wide regulatory dynamics of translation in the Plasmodium falciparum asexual blood stages. eLife 3, e04106 (2014).
  PubMed Central Google Scholar
• Schafer, S. et al. Translational regulation shapes the molecular landscape of complex disease phenotypes. Nat. Commun. 6, 7200 (2015).
  PubMed Google Scholar
• Rooijers, K., Loayza-Puch, F., Nijtmans, L. G. & Agami, R. Ribosome profiling reveals features of normal and disease-associated mitochondrial translation. Nat. Commun. 4, 2886 (2013).
  PubMed Google Scholar
• Zoschke, R., Watkins, K. P. & Barkan, A. A rapid ribosome profiling method elucidates chloroplast ribosome behavior in vivo. Plant Cell 25, 2265–2275 (2013).
  CAS PubMed PubMed Central Google Scholar
• Michel, A. M. et al. GWIPS-viz: development of a ribo-seq genome browser. Nucleic Acids Res. 42, D859–D864 (2014).
  CAS PubMed Google Scholar
• Liu, X., Jiang, H., Gu, Z. & Roberts, J. W. High-resolution view of bacteriophage lambda gene expression by ribosome profiling. Proc. Natl Acad. Sci. USA 110, 11928–11933 (2013).
  CAS PubMed PubMed Central Google Scholar
• Gerashchenko, M. V., Lobanov, A. V. & Gladyshev, V. N. Genome-wide ribosome profiling reveals complex translational regulation in response to oxidative stress. Proc. Natl Acad. Sci. USA 109, 17394–17399 (2012).
  CAS PubMed PubMed Central Google Scholar
• Li, G.-W., Oh, E. & Weissman, J. S. The anti-Shine–Dalgarno sequence drives translational pausing and codon choice in bacteria. Nature 484, 538–541 (2012).
  CAS PubMed PubMed Central Google Scholar
• Woolstenhulme, C. J., Guydosh, N. R., Green, R. & Buskirk, A. R. High-precision analysis of translational pausing by ribosome profiling in bacteria lacking EFP. Cell Rep. 11, 13–21 (2015).
  CAS PubMed PubMed Central Google Scholar
• Chew, G.-L. et al. Ribosome profiling reveals resemblance between long non-coding RNAs and 5′ leaders of coding RNAs. Development 140, 2828–2834 (2013).
  CAS PubMed PubMed Central Google Scholar
• Ingolia, N. T. et al. Ribosome profiling reveals pervasive translation outside of annotated protein-coding genes. Cell Rep. 8, 1365–1379 (2014).
  CAS PubMed PubMed Central Google Scholar
• Andreev, D. E. et al. Oxygen and glucose deprivation induces widespread alterations in mRNA translation within 20 minutes. Genome Biol. 16, 90 (2015).
  PubMed PubMed Central Google Scholar
• Guydosh, N. R. & Green, R. Dom34 rescues ribosomes in 3′ untranslated regions. Cell 156, 950–962 (2014).
  CAS PubMed PubMed Central Google Scholar
• Shalgi, R. et al. Widespread regulation of translation by elongation pausing in heat shock. Mol. Cell 49, 439–452 (2013).
  CAS PubMed PubMed Central Google Scholar
• Han, Y. et al. Ribosome profiling reveals sequence-independent post-initiation pausing as a signature of translation. Cell Res. 24, 842–851 (2014).
  CAS PubMed PubMed Central Google Scholar
• Liu, B., Han, Y. & Qian, S.-B. Cotranslational response to proteotoxic stress by elongation pausing of ribosomes. Mol. Cell 49, 453–463 (2013).
  CAS PubMed PubMed Central Google Scholar
• Subramaniam, A. R., Zid, B. M. & O'Shea, E. K. An integrated approach reveals regulatory controls on bacterial translation elongation. Cell 159, 1200–1211 (2014). This work probes position-specific changes in ribosome distribution among various cellular conditions, concluding that tRNA abundances do not account for elongation rates for most codons, and that pausing of ribosomes during starvation may result in translation abortion.
  CAS PubMed PubMed Central Google Scholar
• Lareau, L. F., Hite, D. H., Hogan, G. J. & Brown, P. O. Distinct stages of the translation elongation cycle revealed by sequencing ribosome-protected mRNA fragments. eLife 3, e01257 (2014). This work identifies a class of short ribosome footprints that may be enriched by treatment with translation elongation inhibitors and that are likely to represent a distinct conformation of the ribosome at a specific stage of the elongation cycle.
  PubMed PubMed Central Google Scholar
• Siegel, A. F., van den Engh, G., Hood, L., Trask, B. & Roach, J. C. Modeling the feasibility of whole genome shotgun sequencing using a pairwise end strategy. Genomics 68, 237–246 (2000).
  CAS PubMed Google Scholar
• Roberts, A., Schaeffer, L. & Pachter, L. Updating RNA-Seq analyses after re-annotation. Bioinformatics 29, 1631–1637 (2013).
  CAS PubMed PubMed Central Google Scholar
• Saliba, A.-E., Westermann, A. J., Gorski, S. A. & Vogel, J. Single-cell RNA-seq: advances and future challenges. Nucleic Acids Res. 42, 8845–8860 (2014).
  CAS PubMed PubMed Central Google Scholar
• Green, R. & Noller, H. F. Ribosomes and translation. Annu. Rev. Biochem. 66, 679–716 (1997).
  CAS PubMed Google Scholar
• Li, G.-W., Burkhardt, D., Gross, C. & Weissman, J. S. Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources. Cell 157, 624–635 (2014).
  CAS PubMed PubMed Central Google Scholar
• Aris, J. P., Klionsky, D. J. & Simoni, R. D. The Fo subunits of the Escherichia coli F1Fo-ATP synthase are sufficient to form a functional proton pore. J. Biol. Chem. 260, 11207–11215 (1985).
  CAS PubMed Google Scholar
• Humphryes, N. et al. The Ecm11–Gmc2 complex promotes synaptonemal complex formation through assembly of transverse filaments in budding yeast. PLoS Genet. 9, e1003194 (2013).
  CAS PubMed PubMed Central Google Scholar
• Lee, M. T. et al. Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition. Nature 503, 360–364 (2013).
  CAS PubMed PubMed Central Google Scholar
• Kronja, I. et al. Widespread changes in the posttranscriptional landscape at the Drosophila oocyte-to-embryo transition. Cell Rep. 7, 1495–1508 (2014).
  CAS PubMed PubMed Central Google Scholar
• Vasquez, J.-J., Hon, C.-C., Vanselow, J. T., Schlosser, A. & Siegel, T. N. Comparative ribosome profiling reveals extensive translational complexity in different Trypanosoma brucei life cycle stages. Nucleic Acids Res. 42, 3623–3637 (2014).
  CAS PubMed PubMed Central Google Scholar
• Stumpf, C. R., Moreno, M. V., Olshen, A. B., Taylor, B. S. & Ruggero, D. The translational landscape of the mammalian cell cycle. Mol. Cell 52, 574–582 (2013).
  CAS PubMed PubMed Central Google Scholar
• Stadler, M. & Fire, A. Conserved translatome remodeling in nematode species executing a shared developmental transition. PLoS Genet. 9, e1003739 (2013).
  PubMed PubMed Central Google Scholar
• Liu, B. & Qian, S.-B. Translational reprogramming in cellular stress response. Wiley Interdiscip. Rev. RNA 5, 301–305 (2014).
  CAS PubMed Google Scholar
• Ingolia, N. T. Ribosome profiling: new views of translation, from single codons to genome scale. Nat. Rev. Genet. 15, 205–213 (2014).
  CAS PubMed Google Scholar
• Michel, A. M. & Baranov, P. V. Ribosome profiling: a Hi-Def monitor for protein synthesis at the genome-wide scale. Wiley Interdiscip. Rev. RNA 4, 473–490 (2013).
  CAS PubMed PubMed Central Google Scholar
• Cox, J. S. & Walter, P. A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response. Cell 87, 391–404 (1996).
  CAS PubMed Google Scholar
• Kannan, K. et al. The general mode of translation inhibition by macrolide antibiotics. Proc. Natl Acad. Sci. USA 111, 15958–15963 (2014).
  CAS PubMed PubMed Central Google Scholar
• Kannan, K., Vázquez-Laslop, N. & Mankin, A. S. Selective protein synthesis by ribosomes with a drug-obstructed exit tunnel. Cell 151, 508–520 (2012).
  CAS PubMed Google Scholar
• Davis, A. R., Gohara, D. W. & Yap, M.-N. F. Sequence selectivity of macrolide-induced translational attenuation. Proc. Natl Acad. Sci. USA 111, 15379–15384 (2014).
  CAS PubMed PubMed Central Google Scholar
• Jung, H., Gkogkas, C. G., Sonenberg, N. & Holt, C. E. Remote control of gene function by local translation. Cell 157, 26–40 (2014).
  CAS PubMed PubMed Central Google Scholar
• Williams, C. C., Jan, C. H. & Weissman, J. S. Targeting and plasticity of mitochondrial proteins revealed by proximity-specific ribosome profiling. Science 346, 748–751 (2014).
  CAS PubMed PubMed Central Google Scholar
• Jan, C. H., Williams, C. C. & Weissman, J. S. Principles of ER cotranslational translocation revealed by proximity-specific ribosome profiling. Science 346, 1257521 (2014).
  PubMed PubMed Central Google Scholar
• Arava, Y. et al. Genome-wide analysis of mRNA translation profiles in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 100, 3889–3894 (2003).
  CAS PubMed PubMed Central Google Scholar
• Heiman, M., Kulicke, R., Fenster, R. J., Greengard, P. & Heintz, N. Cell type-specific mRNA purification by translating ribosome affinity purification (TRAP). Nat. Protoc. 9, 1282–1291 (2014).
  CAS PubMed PubMed Central Google Scholar
• Heiman, M. et al. A translational profiling approach for the molecular characterization of CNS cell types. Cell 135, 738–748 (2008).
  CAS PubMed PubMed Central Google Scholar
• Inada, T. et al. One-step affinity purification of the yeast ribosome and its associated proteins and mRNAs. RNA 8, 948–958 (2002).
  CAS PubMed PubMed Central Google Scholar
• Zanetti, M. E., Chang, I.-F., Gong, F., Galbraith, D. W. & Bailey-Serres, J. Immunopurification of polyribosomal complexes of Arabidopsis for global analysis of gene expression. Plant Physiol. 138, 624–635 (2005).
  CAS PubMed PubMed Central Google Scholar
• Mustroph, A., Zanetti, M. E., Girke, T. & Bailey-Serres, J. Isolation and analysis of mRNAs from specific cell types of plants by ribosome immunopurification. Methods Mol. Biol. 959, 277–302 (2013).
  CAS PubMed Google Scholar
• Thomas, A. et al. A versatile method for cell-specific profiling of translated mRNAs in Drosophila. PLoS ONE 7, e40276 (2012).
  CAS PubMed PubMed Central Google Scholar
• Housley, M. P. et al. Translational profiling through biotinylation of tagged ribosomes in zebrafish. Development 141, 3988–3993 (2014).
  CAS PubMed PubMed Central Google Scholar
• Reinhardt, J. A. & Jones, C. D. Two rapidly evolving genes contribute to male fitness in Drosophila. J. Mol. Evol. 77, 246–259 (2013).
  CAS PubMed Google Scholar
• Starck, S. R. et al. Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I. Science 336, 1719–1723 (2012).
  CAS PubMed Google Scholar
• Rebbapragada, I. & Lykke-Andersen, J. Execution of nonsense-mediated mRNA decay: what defines a substrate? Curr. Opin. Cell Biol. 21, 394–402 (2009).
  CAS PubMed Google Scholar
• Pauli, A., Valen, E. & Schier, A. F. Identifying (non-)coding RNAs and small peptides: challenges and opportunities. BioEssays 37, 103–112 (2015).
  CAS PubMed Google Scholar
• Ulitsky, I. & Bartel, D. P. lincRNAs: genomics, evolution, and mechanisms. Cell 154, 26–46 (2013).
  CAS PubMed PubMed Central Google Scholar
• Kondo, T. et al. Small peptides switch the transcriptional activity of Shavenbaby during Drosophila embryogenesis. Science 329, 336–339 (2010). This paper identifies key roles in fly development for several short peptides (from 11 to 32 amino acids) translated from sORFs on a transcript that was previously thought to be non-coding.
  CAS PubMed Google Scholar
• Magny, E. G. et al. Conserved regulation of cardiac calcium uptake by peptides encoded in small open reading frames. Science 341, 1116–1120 (2013).
  CAS PubMed Google Scholar
• Anderson, D. M. et al. A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell 160, 595–606 (2015).
  CAS PubMed PubMed Central Google Scholar
• Ruiz-Orera, J., Messeguer, X., Subirana, J. A. & Alba, M. M. Long non-coding RNAs as a source of new peptides. eLife 3, e03523 (2014).
  PubMed PubMed Central Google Scholar
• Xu, Y. & Ganem, D. Making sense of antisense: seemingly noncoding RNAs antisense to the master regulator of Kaposi's sarcoma-associated herpesvirus lytic replication do not regulate that transcript but serve as mRNAs encoding small peptides. J. Virol. 84, 5465–5475 (2010).
  CAS PubMed PubMed Central Google Scholar
• Guttman, M., Russell, P., Ingolia, N. T., Weissman, J. S. & Lander, E. S. Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins. Cell 154, 240–251 (2013).
  CAS PubMed PubMed Central Google Scholar
• Carvunis, A.-R. et al. Proto-genes and de novo gene birth. Nature 487, 370–374 (2012). In this work, the authors present evidence to support the protogene hypothesis, according to which new proteins can evolve through the selection and elongation of ORFs encoding peptides translated from putative intergenic transcripts.
  CAS PubMed PubMed Central Google Scholar
• Brubaker, S. W., Gauthier, A. E., Mills, E. W., Ingolia, N. T. & Kagan, J. C. A bicistronic MAVS transcript highlights a class of truncated variants in antiviral immunity. Cell 156, 800–811 (2014).
  CAS PubMed PubMed Central Google Scholar
• Michel, A. M. et al. Observation of dually decoded regions of the human genome using ribosome profiling data. Genome Res. 22, 2219–2229 (2012).
  CAS PubMed PubMed Central Google Scholar
• Noderer, W. L. et al. Quantitative analysis of mammalian translation initiation sites by FACS-seq. Mol. Syst. Biol. 10, 748 (2014).
  PubMed PubMed Central Google Scholar
• Schwaid, A. G. et al. Chemoproteomic discovery of cysteine-containing human short open reading frames. J. Am. Chem. Soc. 135, 16750–16753 (2013).
  CAS PubMed Google Scholar
• Slavoff, S. A. et al. Peptidomic discovery of short open reading frame-encoded peptides in human cells. Nat. Chem. Biol. 9, 59–64 (2013).
  CAS PubMed Google Scholar
• Ma, J. et al. Discovery of human sORF-encoded polypeptides (SEPs) in cell lines and tissue. J. Proteome Res. 13, 1757–1765 (2014).
  CAS PubMed PubMed Central Google Scholar
• Crappé, J. et al. Combining in silico prediction and ribosome profiling in a genome-wide search for novel putatively coding sORFs. BMC Genomics 14, 648 (2013).
  PubMed PubMed Central Google Scholar
• Menschaert, G. et al. Deep proteome coverage based on ribosome profiling aids mass spectrometry-based protein and peptide discovery and provides evidence of alternative translation products and near-cognate translation initiation events. Mol. Cell. Proteomics 12, 1780–1790 (2013).
  CAS PubMed PubMed Central Google Scholar
• Vanderperre, B. et al. Direct detection of alternative open reading frames translation products in human significantly expands the proteome. PLoS ONE 8, e70698 (2013).
  CAS PubMed PubMed Central Google Scholar
• Lin, M. F., Jungreis, I. & Kellis, M. PhyloCSF: a comparative genomics method to distinguish protein coding and non-coding regions. Bioinformatics 27, i275–i282 (2011).
  CAS PubMed PubMed Central Google Scholar
• Huang, H.-Y., Tang, H.-L., Chao, H.-Y., Yeh, L.-S. & Wang, C.-C. An unusual pattern of protein expression and localization of yeast alanyl-tRNA synthetase isoforms. Mol. Microbiol. 60, 189–198 (2006).
  CAS PubMed Google Scholar
• Chang, K.-J. & Wang, C.-C. Translation initiation from a naturally occurring non-AUG codon in Saccharomyces cerevisiae. J. Biol. Chem. 279, 13778–13785 (2004).
  CAS PubMed Google Scholar
• Wan, J. & Qian, S.-B. TISdb: a database for alternative translation initiation in mammalian cells. Nucleic Acids Res. 42, D845–D850 (2014). This work presents a database of alternative translation initiation sites that have been identified by ribosome profiling in mammalian cells.
  CAS PubMed Google Scholar
• Artieri, C. G. & Fraser, H. B. Evolution at two levels of gene expression in yeast. Genome Res. 24, 411–421 (2014).
  CAS PubMed PubMed Central Google Scholar
• Jungreis, I. et al. Evidence of abundant stop codon readthrough in Drosophila and other metazoa. Genome Res. 21, 2096–2113 (2011).
  CAS PubMed PubMed Central Google Scholar
• Schueren, F. et al. Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals. eLife 3, e03640 (2014).
  PubMed PubMed Central Google Scholar
• Jinek, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816–821 (2012).
  CAS PubMed PubMed Central Google Scholar
• Zalatan, J. G. et al. Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds. Cell 160, 339–350 (2015).
  CAS PubMed Google Scholar
• Gilbert, L. A. et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154, 442–451 (2013).
  CAS PubMed PubMed Central Google Scholar
• Gilbert, L. A. et al. Genome-scale CRISPR-mediated control of gene repression and activation. Cell 159, 647–661 (2014).
  CAS PubMed PubMed Central Google Scholar
• Qi, L. S. et al. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell 152, 1173–1183 (2013).
  CAS PubMed PubMed Central Google Scholar