Nonsense-Mediated Decay of Alternative Precursor mRNA Splicing Variants Is a Major Determinant of the <i>Arabidopsis</i> Steady State Transcriptome

Drechsel, Gabriele; Kahles, André; Kesarwani, Anil K.; Stauffer, Eva; Behr, Jonas; Drewe, Philipp; Rätsch, Gunnar; Wachter, Andreas

doi:10.1105/tpc.113.115485

Cited by 192 publications

(256 citation statements)

References 82 publications

(124 reference statements)

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“…For growth on plates, Arabidopsis seeds were treated and grown the same way except that the medium was supplemented with 0.8% (w/v) phytoagar. For translation inhibition, 11-d-old seedlings were transferred to liquid one-half Murashige and Skoog medium containing 2% (w/v) Suc and 10 mg mL -1 cycloheximide and incubated for 4 h at room temperature (equivalent treatment for mock, but in absence of drug; Drechsel et al, 2013).…”

Section: Plant Materials and Growth Conditionsmentioning

confidence: 99%

The Arabidopsis Class II Sirtuin Is a Lysine Deacetylase and Interacts with Mitochondrial Energy Metabolism

et al. 2014

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The posttranslational regulation of proteins by lysine (Lys) acetylation has recently emerged to occur not only on histones, but also on organellar proteins in plants and animals. In particular, the catalytic activities of metabolic enzymes have been shown to be regulated by Lys acetylation. The Arabidopsis (Arabidopsis thaliana) genome encodes two predicted sirtuin-type Lys deacetylases, of which only Silent Information Regulator2 homolog (SRT2) contains a predicted presequence for mitochondrial targeting. Here, we have investigated the function of SRT2 in Arabidopsis. We demonstrate that SRT2 functions as a Lys deacetylase in vitro and in vivo. We show that SRT2 resides predominantly at the inner mitochondrial membrane and interacts with a small number of protein complexes mainly involved in energy metabolism and metabolite transport. Several of these protein complexes, such as the ATP synthase and the ATP/ADP carriers, show an increase in Lys acetylation in srt2 loss-of-function mutants. The srt2 plants display no growth phenotype but rather a metabolic phenotype with altered levels in sugars, amino acids, and ADP contents. Furthermore, coupling of respiration to ATP synthesis is decreased in these lines, while the ADP uptake into mitochondria is significantly increased. Our results indicate that SRT2 is important in fine-tuning mitochondrial energy metabolism.Mitochondria are central hubs of energy metabolism in plants and animals. In addition to a fine-tuned mitochondria-to-nuclear signaling that regulates transcription of nuclear gene expression (Rhoads and Subbaiah, 2007;Schwarzländer et al., 2012), posttranslational modifications of proteins are thought to be essential for the regulation of central metabolic pathways and thus determine the plasticity of plant metabolism (Hartl and Finkemeier, 2012). In mammalian mitochondria, the regulation of metabolic functions by posttranslational

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Section: Plant Materials and Growth Conditionsmentioning

confidence: 99%

The Arabidopsis Class II Sirtuin Is a Lysine Deacetylase and Interacts with Mitochondrial Energy Metabolism

et al. 2014

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“…The control of these alternative splicing differences among different tissues is thought to be the result of differential splicing factor expression and is likely also influenced by tissue-specific methylation patterns (Regulski et al, 2013). Alternative splicing has also been tied closely with nonsensemediated decay (NMD) and has been shown to increase or decrease a transcript's sensitivity to this decay mechanism under a variety of conditions (Kalyna et al, 2012;Drechsel et al, 2013;Staiger and Brown, 2013).…”

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confidence: 99%

Genome-Wide Analysis of Alternative Splicing during Development and Drought Stress in Maize

et al. 2015

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Alternative splicing plays a crucial role in plant development as well as stress responses. Although alternative splicing has been studied during development and in response to stress, the interplay between these two factors remains an open question. To assess the effects of drought stress on developmentally regulated splicing in maize (Zea mays), 94 RNA-seq libraries from ear, tassel, and leaf of the B73 public inbred line were constructed at four developmental stages under both well-watered and drought conditions. This analysis was supplemented with a publicly available series of 53 libraries from developing seed, embryo, and endosperm. More than 48,000 novel isoforms, often with stage-or condition-specific expression, were uncovered, suggesting that developmentally regulated alternative splicing occurs in thousands of genes. Drought induced large developmental splicing changes in leaf and ear but relatively few in tassel. Most developmental stage-specific splicing changes affected by drought were tissue dependent, whereas stage-independent changes frequently overlapped between leaf and ear. A linear relationship was found between gene expression changes in splicing factors and alternative spicing of other genes during development. Collectively, these results demonstrate that alternative splicing is strongly associated with tissue type, developmental stage, and stress condition.After transcription, the majority of eukaryotic premRNA is subjected to a series of posttranscriptional modifications, including the removal of introns to form a mature mRNA (Stamm et al., 2005). Although some introns are removed constitutively, many can be processed in a variety of alternative ways, including exon skipping, intron retention, alternative acceptor, alternative donor, and alternative position (change in both acceptor and donor positions; Lorkovic et al., 2000). These alternative splicing events form a crucial regulatory level and have the ability to alter an mRNA's stability, localization, and protein products. Alternative splicing events are controlled by a variety of cis-elements, including the presence of consensus splice sequences at the intron-exon border and intronic and exonic splicing enhancer sequences (Pertea et al., 2007). Trans-acting factors also exert a strong effect on splicing and are mostly composed of Ser/Arg-rich proteins, which typically promote intron removal, and heterogenous nuclear ribonucleoproteins, which typically inhibit it (Erkelenz et al., 2013). A host of other indirect factors can affect splicing, including transcription rate, methylation status, and any cellular conditions that alter RNA secondary structure (Kornblihtt et al

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“…In addition, the fact that patterns are more apparent for introns that are particularly sensitive to NMD in S. cerevisiae suggests that distinguishing these two classes of genes in other species would be useful for elucidating the predicted patterns. While studies have been conducted in A. thaliana, C. elegans, D. melanogaster, and H. sapiens identifying transcripts that are upregulated in NMD-deficient cells, these studies generally rely on gene expression and do not indicate specifically introns that are particularly sensitive to NMD (Mendell et al 2004;Metzstein and Krasnow 2006;Ramani et al 2009;Drechsel et al 2013).…”

Section: Future Directionsmentioning

confidence: 99%

“…Splicing site consensus sequences are highly conserved and the surrounding nucleotides exhibit weak secondary structure, indicating they are constrained by selection for efficient splicing (Sheth et al 2006;Zafrir and Tuller 2015). In addition, transcripts containing large introns are more dependent on 59-and 39-splicing context to define exons, while splice context in shorter introns appears to be more lax (Jaillon et al 2008;Farlow et al 2012).The nonsense-mediated decay (NMD) pathway is present in all eukaryotes and induces rapid decay of mature mRNAs possessing PTCs, minimizing the effects of splicing errors (Jaillon et al 2008;Ramani et al 2009;Wen and Brogna 2010;Drechsel et al 2013). NMD is expected to select for the presence of an in-frame PTC in an intron so that, if unspliced, the intron will rapidly cause mRNA decay.…”

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confidence: 99%

Selection on Position of Nonsense Codons in Introns

Behringer

Hall

2016

Genetics

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Introns occasionally remain in mature messenger RNAs (mRNAs) due to splicing errors and the translated, aberrant proteins that result represent a metabolic cost and may have other deleterious consequences. The nonsense-mediated decay (NMD) pathway degrades aberrant mRNAs, which it recognizes by the presence of an in-frame premature termination codon (PTC). We investigated whether selection has shaped the location of PTCs in introns to reduce waste and facilitate NMD. We found across seven model organisms, that in both first and last introns, PTCs occur earlier in introns than expected by chance, suggesting that selection favors earlier position. This pattern is more pronounced in species with larger effective population sizes. The pattern does not hold for last introns in the two mammal species, however, perhaps because in these species NMD is not initiated from 39-terminal introns. We conclude that there is compelling evidence that the location of PTCs is shaped by selection for reduced waste and efficient degradation of aberrant mRNAs.KEYWORDS premature termination codon; nonsense-mediated decay; translation; splicing errors; intron definition I T is clear that selection can play a major role in shaping genome architecture (Lynch 2007). Identifying selection is especially straightforward for exons in protein coding genes, where tests based on silent and replacement site substitutions can be employed. However, in noncoding regions, the role of selection in shaping nucleotide content is less easily investigated because of the difficulty identifying expected patterns. In introns, length, phase, and frequency of occurrence have been studied as a product of the processes of selection and drift (Castillo-Davis et al. 2002;Lynch 2002;Whitney and Garland 2010;Kelkar and Ochman 2012) but, apart from sequence-based splicing signals and GC content (Mount 1982;Deutsch and Long 1999;Amit et al. 2012;Farlow et al. 2012), few studies have examined the nucleotide composition of introns (Lim and Burge 2001;Halligan et al. 2004;Andolfatto 2005;Ressayre et al. 2015). In this study, we investigate the role of selection in determining the position of premature termination codons (PTCs) within introns.During post-transcriptional processing, splicing errors can result in introns being present in mature messenger RNAs (mRNAs) (Gilbert 1978). Translation of such mRNAs results in the production of proteins that are aberrant in amino acid sequence and usually shortened. A shorter protein results from the presence of in-frame, PTCs within the unspliced intron, or in a downstream exon due to a frameshift. Aberrant proteins may reduce fitness because they have an activity that is damaging to the cell, and/or because they represent wasted resources, particularly amino acids and sequestered ribosomes (Drummond and Wilke 2009). For these reasons, we hypothesize that selection favors both efficient splicing and mechanisms that minimize the effects of splicing errors.There is strong evidence for selection acting on both the efficiency ...

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Nonsense-Mediated Decay of Alternative Precursor mRNA Splicing Variants Is a Major Determinant of the Arabidopsis Steady State Transcriptome

Cited by 192 publications

References 82 publications

The Arabidopsis Class II Sirtuin Is a Lysine Deacetylase and Interacts with Mitochondrial Energy Metabolism

The Arabidopsis Class II Sirtuin Is a Lysine Deacetylase and Interacts with Mitochondrial Energy Metabolism

Genome-Wide Analysis of Alternative Splicing during Development and Drought Stress in Maize

Selection on Position of Nonsense Codons in Introns

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