Sabrina E Sanchez

Fundación Instituto Leloir, Buenos Aires, Buenos Aires F.D., Argentina

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Publications (11)98.72 Total impact

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    ABSTRACT: Methylation at arginine residues (R) is an important post-translational modification that regulates a myriad of essential cellular processes in eukaryotes, such as transcriptional regulation, RNA processing, signal transduction and DNA repair. Arginine methylation is catalyzed by a family of enzymes known as protein arginine methyltransferases (PRMTs). PRMTs are classified as Type I or Type II, depending on the position of the methyl group on the guanidine of the methylated arginine. Previous reports have linked symmetric R methylation to transcriptional repression, while asymmetric R methylation is generally associated with transcriptional activation. However, global studies supporting this conclusion are not available. Here we compared side by side the physiological and molecular roles of the best characterized plant PRMTs, the Type II PRMT5 and the Type I PRMT4, also known as CARM1 in mammals. We found that prmt5 and prmt4a;4b mutants showed similar alterations in flowering time, photomorphogenic responses and salt stress tolerance, while only prmt5 mutants exhibited alterations in circadian rhythms. An RNA-seq analysis revealed that expression and splicing of many differentially regulated genes was similarly enhanced or repressed by PRMT5 and PRMT4s. Furthermore, PRMT5 and PRMT4s co-regulated the expression and splicing of key regulatory genes associated with transcription, RNA processing, responses to light, flowering, and abiotic stress tolerance, being candidates to mediate the physiological alterations observed in the mutants. Our global analysis indicates that two of the most important Type I and Type II arginine methyltransferases, PRTM4 and PRMT5, have mostly overlapping as well as specific, but not opposite, roles in the global regulation of gene expression in plants.
    Full-text · Article · Dec 2015 · BMC Genomics
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    ABSTRACT: Light modulates plant growth and development to a great extent by regulating gene expression programs. Here we evaluated the effect of light on alternative splicing (AS) in light-grown Arabidopsis thaliana plants using high throughput RNA sequencing (RNA-seq). We found that an acute light pulse given in the middle of the night, a treatment that simulates photoperiod lengthening, affected AS events corresponding to 382 genes. Some of these AS events were associated with genes involved in primary metabolism and stress responses, which may help to adjust metabolic and physiological responses to seasonal changes. We also found that several core clock genes showed changes in AS in response to the light treatment, suggesting that light regulation of AS may play a role in clock entrainment. Finally, we found that many light-regulated AS events were associated with genes encoding RNA processing proteins and splicing factors, supporting the idea that light regulates this post-transcriptional regulatory layer through AS regulation of splicing factors. Interestingly, the effect of a red-light pulse on AS of a gene encoding a splicing factor was not impaired in a quintuple phytochrome mutant, providing unequivocal evidence that non-photosensory photoreceptors control AS in light-grown plants. This article is protected by copyright. All rights reserved.
    Full-text · Article · Nov 2015 · Photochemistry and Photobiology
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    ABSTRACT: The mechanisms by which poikilothermic organisms ensure that biological processes are robust to temperature changes are largely unknown. Temperature compensation, the ability of circadian rhythms to maintain a relatively constant period over the broad range of temperatures resulting from seasonal fluctuations in environmental conditions, is a defining property of circadian networks. Temperature affects the alternative splicing (AS) of several clock genes in fungi, plants, and flies, but the splicing factors that modulate these effects to ensure clock accuracy throughout the year remain to be identified. Here we show that GEMIN2, a spliceosomal small nuclear ribonucleoprotein assembly factor conserved from yeast to humans, modulates low temperature effects on a large subset of pre-mRNA splicing events. In particular, GEMIN2 controls the AS of several clock genes and attenuates the effects of temperature on the circadian period in Arabidopsis thaliana. We conclude that GEMIN2 is a key component of a posttranscriptional regulatory mechanism that ensures the appropriate acclimation of plants to daily and seasonal changes in temperature conditions.
    Full-text · Article · Jul 2015 · Proceedings of the National Academy of Sciences
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    ABSTRACT: Circadian clocks allow organisms to anticipate daily changes in the environment to enhance overall fitness. Transcription factors (TFs) play a prominent role in the molecular mechanism but are incompletely described possibly due to functional redundancy, gene family proliferation, and/or lack of context-specific assays. To overcome these, we performed a high-throughput yeast one-hybrid screen using the LUX ARRYHTHMO (LUX) gene promoter as bait against an Arabidopsis TF library. LUX is a unique gene because its mutation causes severe clock defects and transcript maintains high-amplitude cycling in the cold. We report the well-characterized cold-inducible C-repeat (CRT)/drought-responsive element (DRE) binding factor CBF1/DREB1b is a transcriptional regulator of LUX. We show that CBF1 binds the CRT in the LUX promoter, and both genes overlap in temporal and spatial expression. CBF1 overexpression causes upregulation of LUX and also alters other clock gene transcripts. LUX promoter regions including the CRT and Evening Element (EE) are sufficient for high-amplitude transcriptional cycling in the cold, and cold-acclimated lux seedlings are sensitive to freezing stress. Our data show cold signaling is integrated into the clock by CBF-mediated regulation of LUX expression, thereby defining a new transcriptional mechanism for temperature input to the circadian clock.
    Full-text · Article · Jun 2014 · Current Biology
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    ABSTRACT: Light signaling pathways and the circadian clock interact to help organisms synchronize physiological and developmental processes with periodic environmental cycles. The plant photoreceptors responsible for clock resetting have been characterized, but signaling components that link the photoreceptors to the clock remain to be identified. Here we describe a family of night light-inducible and clock-regulated genes (LNK) that play a key role linking light regulation of gene expression to the control of daily and seasonal rhythms in Arabidopsis thaliana. A genomewide transcriptome analysis revealed that most light-induced genes respond more strongly to light during the subjective day, which is consistent with the diurnal nature of most physiological processes in plants. However, a handful of genes, including the homologous genes LNK1 and LNK2, are more strongly induced by light in the middle of the night, when the clock is most responsive to this signal. Further analysis revealed that the morning phased LNK1 and LNK2 genes control circadian rhythms, photomorphogenic responses, and photoperiodic dependent flowering, most likely by regulating a subset of clock and flowering time genes in the afternoon. LNK1 and LNK2 themselves are directly repressed by members of the TIMING OF CAB1 EXPRESSION/PSEUDO RESPONSE REGULATOR family of core-clock genes in the afternoon and early night. Thus, LNK1 and LNK2 integrate early light signals with temporal information provided by core oscillator components to control the expression of afternoon genes, allowing plants to keep track of seasonal changes in day length.
    No preview · Article · Jul 2013 · Proceedings of the National Academy of Sciences
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    Sabrina E Sanchez · Marcelo J Yanovsky
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    ABSTRACT: The circadian clock of Arabidopsis, a popular model organism for plants, is more complex than expected, with negative feedback loops based on the repression of gene expression having a less exclusive role than previously thought.
    Full-text · Article · Apr 2013 · eLife Sciences
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    ABSTRACT: Alternative splicing (AS) allows the production of multiple mRNA variants from a single gene, which contributes to increase the complexity of the proteome. There is evidence that AS is regulated not only by auxiliary splicing factors, but also by components of the core spliceosomal machinery, as well as through epigenetic modifications. However, to what extent these different mechanisms contribute to the regulation of AS in response to endogenous or environmental stimuli is still unclear. Circadian clocks allow organisms to adjust physiological processes to daily changes in environmental conditions. Here we review recent evidence linking circadian clock and AS, and discuss the role of Protein Arginine Methyltransferase 5 (PRMT5) in these processes. We propose that the interactions between daily oscillations in AS and circadian rhythms in the expression of splicing factors and epigenetic regulators offer a great opportunity to dissect the contribution of these mechanisms to the regulation of AS in a physiologically relevant context.
    Full-text · Article · Nov 2011 · RNA biology
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    ABSTRACT: Circadian clocks allow organisms to adjust multiple physiological and developmental processes in anticipation of daily and seasonal changes in the environment. At the molecular level these clocks consist of interlocked feedback loops, involving transcriptional activation and repression, but also post-translational modifications. In a recently published work we provided evidence that PRMT5, a protein arginine methyl transferase, is part of a novel loop within the circadian clock of the plant Arabidopsis thaliana by regulating alternative splicing of key clock mRNAs. We also found evidence indicating that PRMT5 has a role in the regulation of alternative splicing and the circadian network in Drosophila melanogaster, although the clock connection in the latter is more elusive and seems to be at the output level. We conclude that alternative precursor messenger RNA (premRNA) splicing is part of the circadian program and could be a main actor in the fine-tuning of biological clocks. Here, we embrace the alternative splicing process as part of the circadian program and discuss the possibility that this mechanism is of fundamental relevance for the fine-tuning of biological clocks.
    Full-text · Article · May 2011 · Communicative & integrative biology
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    ABSTRACT: When plants become shaded by neighbouring plants, they perceive a decrease in the red/far-red (R/FR) ratio of the light environment, which provides an early and unambiguous warning of the presence of competing vegetation. The mechanistic bases of the natural genetic variation in response to shade signals remain largely unknown. This study demonstrates that a wide range of genetic variation for hypocotyl elongation in response to an FR pulse at the end of day (EOD), a light signal that simulates natural shade, exists between Arabidopsis accessions. A quantitative trait locus (QTL) mapping analysis was done in the Bayreuth×Shahdara recombinant inbred line population. EODINDEX1 is the most significant QTL identified in response to EOD. The Shahdara alleles at EODINDEX1 caused a reduced response to shade as a consequence of an impaired hypocotyl inhibition under white light, and an accelerated leaf movement rhythm, which correlated positively with the pattern of circadian expression of clock genes such as PRR7 and PRR9. Genetic and quantitative complementation analyses demonstrated that ELF3 is the most likely candidate gene underlying natural variation at EODINDEX1. In conclusion, ELF3 is proposed as a component of the shade avoidance signalling pathway responsible for the phenotypic differences between Arabidopsis populations in relation to adaptation in a changing light environment.
    Full-text · Article · Jan 2011 · Journal of Experimental Botany
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    ABSTRACT: In many plant species, the duration of the daily exposure to light (photoperiod) provides a seasonal cue that helps to adjust flowering time to the most favourable time of the year. In Arabidopsis thaliana, the core mechanism of acceleration of flowering by long days involves the stabilisation of the CONSTANS (CO) protein by light reaching the leaves, the direct induction of the expression of FLOWERING LOCUS T (FT) by CO and the migration of FT to the apex to promote flowering. In rice (Oryza sativa), the promotion of flowering by short days depends on the interplay between light conditions, and the genes Grain number, plant height and heading date locus 7 (Ghd7) and Early heading date 1 (Ehd1). In both cases, other day length-induced changes reinforce the core photoperiodic pathway of promotion of flowering. However, there are regulators of flowering time, quantitatively less important than the core pathways but still significant, which impact in the opposite direction, i.e. favouring rice flowering under long days or Arabidopsis flowering under short days. We show, for instance, that short days enhance leaf expression of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 3 (SPL3), which stimulates Arabidopsis flowering under these conditions. We propose that fine tuning of flowering time depends on the balance of a hierarchy of multiple points of action of photoperiod on the network controlling flowering.
    Full-text · Article · Dec 2010 · Photochemical and Photobiological Sciences
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    ABSTRACT: Circadian rhythms allow organisms to time biological processes to the most appropriate phases of the day-night cycle. Post-transcriptional regulation is emerging as an important component of circadian networks, but the molecular mechanisms linking the circadian clock to the control of RNA processing are largely unknown. Here we show that PROTEIN ARGININE METHYL TRANSFERASE 5 (PRMT5), which transfers methyl groups to arginine residues present in histones and Sm spliceosomal proteins, links the circadian clock to the control of alternative splicing in plants. Mutations in PRMT5 impair several circadian rhythms in Arabidopsis thaliana and this phenotype is caused, at least in part, by a strong alteration in alternative splicing of the core-clock gene PSEUDO RESPONSE REGULATOR 9 (PRR9). Furthermore, genome-wide studies show that PRMT5 contributes to the regulation of many pre-messenger-RNA splicing events, probably by modulating 5'-splice-site recognition. PRMT5 expression shows daily and circadian oscillations, and this contributes to the mediation of the circadian regulation of expression and alternative splicing of a subset of genes. Circadian rhythms in locomotor activity are also disrupted in dart5-1, a mutant affected in the Drosophila melanogaster PRMT5 homologue, and this is associated with alterations in splicing of the core-clock gene period and several clock-associated genes. Our results demonstrate a key role for PRMT5 in the regulation of alternative splicing and indicate that the interplay between the circadian clock and the regulation of alternative splicing by PRMT5 constitutes a common mechanism that helps organisms to synchronize physiological processes with daily changes in environmental conditions.
    Full-text · Article · Oct 2010 · Nature

Publication Stats

211 Citations
98.72 Total Impact Points

Institutions

  • 2015
    • Fundación Instituto Leloir
      Buenos Aires, Buenos Aires F.D., Argentina
  • 2014-2015
    • University of Southern California
      • Division of Molecular and Computational Biology
      Los Ángeles, California, United States
  • 2010
    • National Scientific and Technical Research Council
      Buenos Aires, Buenos Aires F.D., Argentina