Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Gene expression regulation relies on a variety of molecular mechanisms affecting different steps of a messenger RNA (mRNA) life: transcription, processing, splicing, alternative splicing, transport, translation, storage and decay. Light induces massive reprogramming of gene expression in plants. Differences in alternative splicing patterns in response to environmental stimuli suggest that alternative splicing plays an important role in plant adaptation to changing life conditions. In a recent publication, our laboratories showed that light regulates alternative splicing of a subset of Arabidopsis genes encoding proteins involved in RNA processing by chloroplast retrograde signals. The light effect on alternative splicing is also observed in roots when the communication with the photosynthetic tissues is not interrupted, suggesting that a signaling molecule travels through the plant. These results point at alternative splicing regulation by retrograde signals as an important mechanism for plant adaptation to their environment. © Ezequiel Petrillo, Micaela A Godoy Herz, Andrea Barta, Maria Kalyna, and Alberto R Kornblihtt.

Registro:

Documento: Artículo
Título:Let there be light: Regulation of gene expression in plants
Autor:Petrillo, E.; Herz, M.A.G.; Barta, A.; Kalyna, M.; Kornblihtt, A.R.
Filiación:Max F. Perutz Laboratories, Medical University of Vienna, Vienna, Austria
Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular IFIBYNE-CONICET, Pabellón 2, Buenos Aires, Argentina
Department of Applied Genetics and Cell Biology, BOKU - University of Natural Resources and Life Sciences, Vienna, Austria
Palabras clave:Alternative splicing; Chloroplast; Light; Photoreceptors; Retrograde signaling; RNA; messenger RNA; alternative RNA splicing; evolutionary adaptation; gene expression regulation; genetic transcription; nonhuman; plant; Review; signal transduction; Arabidopsis
Año:2014
Volumen:11
Número:10
Página de inicio:1220
Página de fin:1225
DOI: http://dx.doi.org/10.4161/15476286.2014.972852
Título revista:RNA Biology
Título revista abreviado:RNA Biol.
ISSN:15476286
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15476286_v11_n10_p1220_Petrillo

Referencias:

  • Perales, R., Bentley, D., Cotranscriptionality: The transcription elongation complex as a nexus for nuclear transactions (2009) Mol Cell, 36, pp. 178-191. , http://dx.doi.org/10.1016/j.molcel.2009.09.018, PMID:19854129
  • Kornblihtt, A.R., Schor, I.E., Alló, M., Dujardin, G., Petrillo, E., Muñoz, M.J., Alternative splicing: A pivotal step between eukaryotic transcription and translation (2013) Nat. Rev. Mol. Cell Biol., 14 (3), pp. 153-165. , http://dx.doi.org/10.1038/nrm3525, PMID:23385723
  • Reddy, A.S., Marquez, Y., Kalyna, M., Barta, A., Complexity of the alternative splicing landscape in plants (2013) Plant Cell, 25 (10), pp. 3657-3683. , http://dx.doi.org/10.1105/tpc.113.117523, PMID:24179125
  • Kalyna, M., Simpson, C.G., Syed, N.H., Lewandowska, D., Marquez, Y., Kusenda, B., Marshall, J., McNicol, J., Alternative splicing and nonsensemediated decay modulate expression of important regulatory genes in Arabidopsis (2012) Nucleic Acids Res, 40 (6), pp. 2454-2469. , http://dx.doi.org/10.1093/nar/gkr932, PMID:22127866
  • Kornblihtt, A.R., Schor, I.E., Allo, M., Blencowe, B.J., When chromatin meets splicing (2009) Nat. Struct. Mol. Biol, 16 (9), pp. 902-903. , http://dx.doi.org/10.1038/nsmb0909-902, PMID:19739285
  • Tilgner, H., Knowles, D.G., Johnson, R., Davis, C.A., Chakrabortty, S., Djebali, S., Curado, J., Guigó, R., Deep sequencing of subcellular RNA fractions shows splicing to be predominantly co-transcriptional in the human genome but inefficient for lncRNAs (2012) Genome Res., 22, pp. 1616-1625. , http://dx.doi.org/10.1101/gr.134445.111, PMID:22955974
  • Luco, R.F., Allo, M., Schor, I.E., Kornblihtt, A.R., Misteli, T., Epigenetics in alternative pre-mRNA splicing (2011) Cell, 144 (1), pp. 16-26. , http://dx.doi.org/10.1016/j.cell.2010.11.056, PMID:21215366
  • Gómez Acuña, L.I., Kornblihtt, A.R., Long range chromatin organization: A new layer in splicing regulation? (2014) Transcription, 5. , PMID:24802896
  • De La Mata, M., Alonso, C.R., Kadener, S., Fededa, J.P., Blaustein, M., Pelisch, F., Cramer, P., Kornblihtt, A.R., A slow RNA polymerase II affects alternative splicing in vivo (2003) Mol Cell, 12 (2), pp. 525-532. , PMID:14536091
  • Dujardin, G., Lafaille, C., De La Mata, M., Marasco, L.E., Muñoz, M.J., Le Jossic-Corcos, C., Corcos, L., Kornblihtt, A.R., How slow RNA polymerase II elongation favors alternative exon skipping (2014) Mol. Cell, 54 (4), pp. 683-690. , http://dx.doi.org/10.1016/j.molcel.2014.03.044, PMID:24793692
  • Marquez, Y., Brown, J.W., Simpson, C., Barta, A., Kalyna, M., Transcriptome survey reveals increased complexity of the alternative splicing landscape in Arabidopsis (2012) Genome Res, 22 (6), pp. 1184-1195. , http://dx.doi.org/10.1101/gr.134106.111, PMID:22391557
  • Pan, Q., Shai, O., Lee, L.J., Frey, B.J., Blencowe, B.J., Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing (2008) Nat Genet, 40, pp. 1413-1415. , http://dx.doi.org/10.1038/ng.259, PMID:18978789
  • Kornblihtt, A.R., A long noncoding way to alternative splicing in plant development (2014) Dev Cell, 30, pp. 117-119. , http://dx.doi.org/10.1016/j.devcel.2014.07.010, in press
  • Staiger, D., Brown, J.W., Alternative splicing at the intersection of biological timing, development, and stress responses (2013) Plant Cell, 25 (10), pp. 3640-3656. , http://dx.doi.org/10.1105/tpc.113.113803, PMID:24179132
  • Ding, F., Cui, P., Wang, Z., Zhang, S., Ali, S., Xiong, L., Genome-wide analysis of alternative splicing of premRNA under salt stress in Arabidopsis (2014) BMC Genomics, 15, p. 431. , http://dx.doi.org/10.1186/1471-2164-15-431, PMID:24897929
  • Petrillo, E., Godoy Herz, M.A., Fuchs, A., Reifer, D., Fuller, J., Yanovsky, M.J., Simpson, C., Kalyna, M., A chloroplast retrograde signal regulates nuclear alternative splicing (2014) Science, 344 (6182), pp. 427-430. , http://dx.doi.org/10.1126/science.1250322, PMID:24763593
  • Baena-González, E., Energy signaling in the regulation of gene expression during stress (2010) Mol Plant, 3, pp. 300-313. , PMID:20080814
  • Lauria, M., Rossi, V., Epigenetic control of gene regulation in plants (2011) Biochim Biophys Acta, 1809, pp. 369-378. , http://dx.doi.org/10.1016/j.bbagrm.2011.03.002, PMID:21414429
  • Floris, M., Mahgoub, H., Lanet, E., Robaglia, C., Menand, B., Post-transcriptional regulation of gene expression in plants during abiotic stress (2009) Int J Mol Sci, 10, pp. 3168-3185. , http://dx.doi.org/10.3390/ijms10073168, PMID:19742130
  • Schmoll, M., Tian, C., Sun, J., Tisch, D., Glass, N., Unravelling the molecular basis for light modulated cellulase gene expression - The role of photoreceptors in Neurospora crassa (2012) BMC Genomics, 13, p. 127. , http://dx.doi.org/10.1186/1471-2164-13-127, PMID:22462823
  • Jiao, Y., Lau, O.S., Deng, X.W., Light-regulated transcriptional networks in higher plants (2007) Nat Rev Genet, 8, pp. 217-230. , http://dx.doi.org/10.1038/nrg2049, PMID:17304247
  • Kami, C., Lorrain, S., Hornitschek, P., Fankhauser, C., Light-regulated plant growth and development (2010) Curr Top Dev Biol, 91, pp. 29-66. , http://dx.doi.org/10.1016/S0070-2153(10)91002-8, PMID:20705178
  • Casal, J.J., Photoreceptor signaling networks in plant responses to shade (2013) Annu Rev Plant Biol, 64, pp. 403-427. , http://dx.doi.org/10.1146/annurev-arplant-050312-120221, PMID:23373700
  • Strasser, B., Sánchez-Lamas, M., Yanovsky, M.J., Casal, J.J., Cerdán, P.D., Arabidopsis thaliana life without phytochromes (2010) PNAS, 107, pp. 4776-4781. , http://dx.doi.org/10.1073/pnas.0910446107, PMID: 20176939
  • Woodson, J., Chory, J., Coordination of gene expression between organellar and nuclear genomes (2008) Nat Rev Genet, 9, pp. 383-395. , http://dx.doi.org/10.1038/nrg2348, PMID:18368053
  • Ruckle, M.E., Burgoon, L.D., Lawrence, L.A., Sinkler, C.A., Larkin, R.M., Plastids are major regulators of light signaling in Arabidopsis (2012) Plant Phys, 159, pp. 366-390. , http://dx.doi.org/10.1104/pp.112.193599, PMID:22383539
  • Chan, K., Crisp, P., Estavillo, G., Pogson, B., Chloroplast-to-nucleus communication: Current knowledge, experimental strategies and relationship to drought stress signaling (2010) Plant Signal Behav, 5, pp. 1575-1582. , http://dx.doi.org/10.4161/psb.5.12.13758, PMID: 21512326
  • Jarvis, P., López-Juez, E., Biogenesis and homeostasis of chloroplasts and other plastids (2013) Nature Reviews Mol Cell Biol, 14, pp. 787-802. , http://dx.doi.org/10.1038/nrm3702, PMID:24263360
  • Foyer, C.H., Neukermans, J., Queval, G., Noctor, G., Harbinson, J., Photosynthetic control of electron transport and the regulation of gene expression (2012) J Exp Bot, 63, pp. 1637-1661. , http://dx.doi.org/10.1093/jxb/ers013, PMID:22371324
  • Terry, M., Smith, A., A model for tetrapyrrole synthesis as the primary mechanism for plastid-to-nucleus signaling during chloroplast biogenesis (2013) Front Plant Sci, 4, p. 14. , http://dx.doi.org/10.3389/fpls.2013.00014, PMID:23407626
  • Szechyńska-Hebda, M., Karpiński, S., Light intensity-dependent retrograde signalling in higher plants (2013) J Plant Phys, 170, pp. 1501-1516. , http://dx.doi.org/10.1016/j.jplph.2013.06.005, PMID:23850030
  • Piippo, M., Allahverdiyeva, Y., Paakkarinen, V., Suoranta, U.-M., Battchikova, N., Aro, E.-M., Chloroplast-mediated regulation of nuclear genes in Arabidopsis thaliana in the absence of light stress (2006) Physiol Genomics, 25, pp. 142-152. , PMID:16403842
  • Pfannschmidt, T., Chloroplast redox signals: How photosynthesis controls its own genes (2003) Trends Plant Sci, 8, pp. 33-41. , http://dx.doi.org/10.1016/S1360-1385(02)00005-5, PMID:12523998
  • Karpinski, S., Escobar, C., Karpinska, B., Creissen, G., Mullineaux, P.M., Photosynthetic electron transport regulates the expression of cytosolic ascorbate peroxidase genes in Arabidopsis during excess light stress (1997) Plant Cell, 9, pp. 627-640. , http://dx.doi.org/10.1105/tpc.9.4.627, PMID:9144965
  • Pfalz, J., Liebers, M., Hirth, M., Grübler, B., Holtzegel, U., Schröter, Y., Dietzel, L., Pfannschmidt, T., Environmental control of plant nuclear gene expression by chloroplast redox signals (2012) Front Plant Sci, 3, p. 257. , http://dx.doi.org/10.3389/fpls.2012.00257, PMID:23181068
  • Bräutigam, K., Dietzel, L., Kleine, T., Ströher, E., Wormuth, D., Dietz, K.-J.J., Radke, D., Dörmann, P., Dynamic plastid redox signals integrate gene expression and metabolism to induce distinct metabolic states in photosynthetic acclimation in Arabidopsis (2009) Plant Cell, 21, pp. 2715-2732. , http://dx.doi.org/10.1105/tpc.108.062018, PMID:19737978
  • Fey, V., Wagner, R., Braütigam, K., Wirtz, M., Hell, R., Dietzmann, A., Leister, D., Pfannschmidt, T., Retrograde plastid redox signals in the expression of nuclear genes for chloroplast proteins of Arabidopsis thaliana (2005) JBC, 280, pp. 5318-5328. , http://dx.doi.org/10.1074/jbc.M406358200, PMID:15561727
  • Petracek, M.E., Dickey, L.F., Huber, S.C., Thompson, W.F., Light-regulated changes in abundance and polyribosome association of ferredoxin mRNA are dependent on photosynthesis (1997) Plant Cell, 9, pp. 2291-2300. , http://dx.doi.org/10.1105/tpc.9.12.2291, PMID:9437868
  • Gadjev, I., Vanderauwera, S., Gechev, T.S., Laloi, C., Minkov, I.N., Shulaev, V., Apel, K., Breusegem, F., Transcriptomic footprints disclose specificity of reactive oxygen species signaling in Arabidopsis (2006) Plant Phys, 141, pp. 436-445. , PMID:16603662
  • Scarpeci, T.E., Zanor, M.I., Carrillo, N., Mueller-Roeber, B., Valle, E.M., Generation of superoxide anion in chloroplasts of Arabidopsis thaliana during active photosynthesis: A focus on rapidly induced genes (2008) Plant Mol Biol, 66, pp. 361-378. , http://dx.doi.org/10.1007/s11103-007-9274-4, PMID:18158584
  • Suzuki, N., Koussevitzky, S., Mittle, R., Miller, G., ROS and redox signalling in the response of plants to abiotic stress (2012) Plant Cell Environ, 35 (2), pp. 259-270. , http://dx.doi.org/10.1111/j.1365-3040.2011.02336.x, PMID:21486305
  • Karpinski, S., Reynolds, H., Karpinska, B., Wingsle, G., Creissen, G., Mullineaux, P., Systemic signaling and acclimation in response to excess excitation energy in Arabidopsis (1999) Science, 284 (5414), pp. 654-657. , http://dx.doi.org/10.1126/science.284.5414.654, PMID:10213690
  • Karpinski, S., Gabrys, H., Mateo, A., Karpinska, B., Mullineaux, P., Light perception in plant disease defence signalling (2003) Curr Opin Plant Biol, 6, pp. 390-396. , http://dx.doi.org/10.1016/S1369-5266(03)00061-X, PMID:12873535
  • Ruckle, M.E., Larkin, R.M., Plastid signals that affect photomorphogenesis in Arabidopsis thaliana are dependent on GENOMES UNCOUPLED 1 and cryptochrome1 (2009) New Phytol, 182, pp. 367-379. , http://dx.doi.org/10.1111/j.1469-8137.2008.02729.x, PMID:19140931
  • Ruckle, M.E., DeMarco, S.M., Larkin, R.M., Plastid signals remodel light signaling networks and are essential for efficient chloroplast biogenesis in Arabidopsis (2007) Plant Cell, 19, pp. 3944-3960. , http://dx.doi.org/10.1105/tpc.107.054312, PMID:18065688
  • Lepistö, A., Rintamäki, E., Coordination of plastid and light signaling pathways upon development of Arabidopsis leaves under various photoperiods (2012) Mol Plant, 5, pp. 799-816. , http://dx.doi.org/10.1093/mp/ssr106, PMID:22199239
  • Ma, L., Li, J., Qu, L., Hager, J., Chen, Z., Zhao, H., Deng, X.W., Light control of Arabidopsis development entails coordinated regulation of genome expression and cellular pathways (2001) Plant Cell, 13, pp. 2589-2607. , http://dx.doi.org/10.1105/tpc.13.12.2589, PMID:11752374
  • Jiao, Y., Ma, L., Strickland, E., Deng, X.W., Conservation and divergence of light-regulated genome expression patterns during seedling development in rice and Arabidopsis (2005) Plant Cell, 17, pp. 3239-3256. , http://dx.doi.org/10.1105/tpc.105.035840, PMID:16284311
  • Casal, J.J., Yanovsky, M.J., Regulation of gene expression by light (2005) Int J Dev Biol, 49, pp. 501-511. , http://dx.doi.org/10.1387/ijdb.051973jc, PMID:16096960
  • Fisher, A.J., Franklin, K.A., Chromatin remodelling in plant light signalling (2011) Physiol Plant, 142, pp. 305-313. , http://dx.doi.org/10.1111/j.1399-3054.2011.01476.x, PMID:21457270
  • Guo, L., Zhou, J., Elling, A.A., Charron, J.B., Deng, X.W., Histone modifications and expression of light-regulated genes in Arabidopsis are cooperatively influenced by changing light conditions (2008) Plant Phys, 147, pp. 2070-2083. , http://dx.doi.org/10.1104/pp.108.122929, PMID:18550682
  • Mano, S., Yamaguchi, K., Hayashi, M., Nishimura, M., Stromal and thylakoid-bound ascorbate peroxidases are produced by alternative splicing in pumpkin FEBS Lett, 413, pp. 21-26. , http://dx.doi.org/10.1016/S0014-5793(97)00862-4, PMID:9287110
  • Mano, S., Hayashi, M., Nishimura, M., Light regulates alternative splicing of hydroxypyruvate reductase in pumpkin (1999) Plant J, 17, pp. 309-320. , http://dx.doi.org/10.1046/j.1365-313X.1999.00378.x, PMID:10097389
  • Sanchez, S.E., Petrillo, E., Beckwith, E.J., Zhang, X., Rugnone, M.L., Hernando, C.E., Cuevas, J.C., Simpson, C.G., A methyl transferase links the circadian clock to the regulation of alternative splicing (2010) Nature, 468 (7320), pp. 112-116. , http://dx.doi.org/10.1038/nature09470, PMID:20962777
  • Wang, X., Wu, F., Xie, Q., Wang, H., Wang, Y., Yue, Y., Gahura, O., Cao, Y., SKIP is a component of the spliceosome linking alternative splicing and the circadian clock in Arabidopsis (2012) Plant Cell, 24, pp. 3278-3295. , http://dx.doi.org/10.1105/tpc.112.100081, PMID:22942380
  • Simpson, C.G., Fuller, J., Maronova, M., Kalyna, M., Davidson, D., McNicol, J., Barta, A., Brown, J.W., Monitoring changes in alternative precursor messenger RNA splicing in multiple gene transcripts (2008) Plant J, 53, pp. 1035-1048. , http://dx.doi.org/10.1111/j.1365-313X.2007.03392.x, PMID:18088312
  • Tanabe, N., Yoshimura, K., Kimura, A., Yabuta, Y., Shigeoka, S., Differential Expression of Alternatively Spliced mRNAs of Arabidopsis SR Protein Homologs, atSR30 and atSR45a, in Response to Environmental Stress (2007) Plant Cell Phys, 48, pp. 1036-1049. , http://dx.doi.org/10.1093/pcp/pcm069, PMID:17556373
  • Shikata, H., Shibata, M., Ushijima, T., Nakashima, M., Kong, S.-G., Matsuoka, K., Lin, C., Matsushita, T., The RS domain of Arabidopsis splicing factor RRC1 is required for phytochrome B signal transduction (2012) Plant J, 70, pp. 727-738. , http://dx.doi.org/10.1111/j.1365-313X.2012.04937.x, PMID:22324426
  • Wu, H.-P., Su, Y.-S., Chen, H.-C., Chen, Y.-R., Wu, C.-C., Lin, W.-D., Tu, S.-L., Genome-wide analysis of light-regulated alternative splicing mediated by photoreceptors in Physcomitrella patens (2014) Genome Biol, 15, p. R10. , http://dx.doi.org/10.1186/gb-2014-15-1-r10, PMID:24398233
  • Falciatore, A., Merendino, L., Barneche, F., Ceol, M., Meskauskiene, R., Apel, K., Rochaix, J.-D., The FLP proteins act as regulators of chlorophyll synthesis in response to light and plastid signals in Chlamydomonas (2005) Genes Dev, 19, pp. 176-187. , http://dx.doi.org/10.1101/gad.321305, PMID:15630026
  • Lopato, S., Waigmann, E., Barta, A., Characterization of a novel arginine/serine-rich splicing factor in Arabidopsis (1996) Plant Cell, 8, pp. 2255-2264. , http://dx.doi.org/10.1105/tpc.8.12.2255, PMID:8989882
  • Arsova, B., Hoja, U., Wimmelbacher, M., Greiner, E., Ustün, S., Melzer, M., Petersen, K., Börnke, F., Plastidial thioredoxin z interacts with two fructokinaselike proteins in a thiol-dependent manner: Evidence for an essential role in chloroplast development in Arabidopsis and Nicotiana benthamiana (2010) Plant Cell, 22, pp. 1498-1515. , http://dx.doi.org/10.1105/tpc.109.071001, PMID:20511297
  • Barajas-López, J., Blanco, N., Strand, A˚., Plastid-to-nucleus communication, signals controlling the running of the plant cell (2013) Biochim. Biophys. Acta, 1833, pp. 425-437. , http://dx.doi.org/10.1016/j.bbamcr.2012.06.020, PMID:22749883
  • Estavillo, G.M., Crisp, P.A., Pornsiriwong, W., Wirtz, M., Collinge, D., Carrie, C., Giraud, E., Javot, H., Evidence for a SAL1-PAP chloroplast retrograde pathway that functions in drought and high light signaling in Arabidopsis (2011) Plant Cell, 23, pp. 3992-4012. , http://dx.doi.org/10.1105/tpc.111.091033, PMID:22128124
  • Sun, X., Feng, P., Xu, X., Guo, H., Ma, J., Chi, W., Lin, R., Zhang, L., A chloroplast envelope-bound PHD transcription factor mediates chloroplast signals to the nucleus (2011) Nat. Commun, 2, p. 477. , http://dx.doi.org/10.1038/ncomms1486, PMID:21934661
  • Rolland, F., Baena-Gonzalez, E., Sheen, J., Sugar sensing and signaling in plants: Conserved and novel mechanisms (2006) Annu Rev Plant Biol, 57, pp. 675-709. , http://dx.doi.org/10.1146/annurev.arplant.57.032905.105441, PMID:16669778
  • Hausler, R., Heinrichs, L., Schmitz, J., Flugge, U., How Sugars Might Coordinate Chloroplast and Nuclear Gene Expression during Acclimation to High Light Intensities (2014) Mol Plant, 7, pp. 1121-1137. , http://dx.doi.org/10.1093/mp/ssu064, PMID:25006007
  • Blanco, N.E., Guinea-Díaz, M., Whelan, J., Strand, A˚., Interaction between plastid and mitochondrial retrograde signalling pathways during changes to plastid redox status (2014) Phil Trans R Soc B, 369, p. 20130231. , http://dx.doi.org/10.1098/rstb.2013.0231, PMID:24591717

Citas:

---------- APA ----------
Petrillo, E., Herz, M.A.G., Barta, A., Kalyna, M. & Kornblihtt, A.R. (2014) . Let there be light: Regulation of gene expression in plants. RNA Biology, 11(10), 1220-1225.
http://dx.doi.org/10.4161/15476286.2014.972852
---------- CHICAGO ----------
Petrillo, E., Herz, M.A.G., Barta, A., Kalyna, M., Kornblihtt, A.R. "Let there be light: Regulation of gene expression in plants" . RNA Biology 11, no. 10 (2014) : 1220-1225.
http://dx.doi.org/10.4161/15476286.2014.972852
---------- MLA ----------
Petrillo, E., Herz, M.A.G., Barta, A., Kalyna, M., Kornblihtt, A.R. "Let there be light: Regulation of gene expression in plants" . RNA Biology, vol. 11, no. 10, 2014, pp. 1220-1225.
http://dx.doi.org/10.4161/15476286.2014.972852
---------- VANCOUVER ----------
Petrillo, E., Herz, M.A.G., Barta, A., Kalyna, M., Kornblihtt, A.R. Let there be light: Regulation of gene expression in plants. RNA Biol. 2014;11(10):1220-1225.
http://dx.doi.org/10.4161/15476286.2014.972852