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Author

Martin Kupiec

Bio: Martin Kupiec is an academic researcher from Tel Aviv University. The author has contributed to research in topics: DNA repair & Saccharomyces cerevisiae. The author has an hindex of 52, co-authored 194 publications receiving 11950 citations. Previous affiliations of Martin Kupiec include Weizmann Institute of Science & Hebrew University of Jerusalem.


Papers
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Journal ArticleDOI
10 May 2012-Nature
TL;DR: The findings suggest that RNA decoration by m6A has a fundamental role in regulation of gene expression, and a subset of stimulus-dependent, dynamically modulated sites is identified.
Abstract: An extensive repertoire of modifications is known to underlie the versatile coding, structural and catalytic functions of RNA, but it remains largely uncharted territory. Although biochemical studies indicate that N(6)-methyladenosine (m(6)A) is the most prevalent internal modification in messenger RNA, an in-depth study of its distribution and functions has been impeded by a lack of robust analytical methods. Here we present the human and mouse m(6)A modification landscape in a transcriptome-wide manner, using a novel approach, m(6)A-seq, based on antibody-mediated capture and massively parallel sequencing. We identify over 12,000 m(6)A sites characterized by a typical consensus in the transcripts of more than 7,000 human genes. Sites preferentially appear in two distinct landmarks--around stop codons and within long internal exons--and are highly conserved between human and mouse. Although most sites are well preserved across normal and cancerous tissues and in response to various stimuli, a subset of stimulus-dependent, dynamically modulated sites is identified. Silencing the m(6)A methyltransferase significantly affects gene expression and alternative splicing patterns, resulting in modulation of the p53 (also known as TP53) signalling pathway and apoptosis. Our findings therefore suggest that RNA decoration by m(6)A has a fundamental role in regulation of gene expression.

3,237 citations

Journal ArticleDOI
TL;DR: It is testified that in endogenous genes, folding energy affects translation efficiency in a global manner that is not related to the expression levels of individual genes, and thus cannot be detected by correlation with their expression levels.
Abstract: Synonymous mutations do not alter the protein produced yet can have a significant effect on protein levels. The mechanisms by which this effect is achieved are controversial; although some previous studies have suggested that codon bias is the most important determinant of translation efficiency, a recent study suggested that mRNA folding at the beginning of genes is the dominant factor via its effect on translation initiation. Using the Escherichia coli and Saccharomyces cerevisiae transcriptomes, we conducted a genome-scale study aiming at dissecting the determinants of translation efficiency. There is a significant association between codon bias and translation efficiency across all endogenous genes in E. coli and S. cerevisiae but no association between folding energy and translation efficiency, demonstrating the role of codon bias as an important determinant of translation efficiency. However, folding energy does modulate the strength of association between codon bias and translation efficiency, which is maximized at very weak mRNA folding (i.e., high folding energy) levels. We find a strong correlation between the genomic profiles of ribosomal density and genomic profiles of folding energy across mRNA, suggesting that lower folding energies slow down the ribosomes and decrease translation efficiency. Accordingly, we find that selection forces act near uniformly to decrease the folding energy at the beginning of genes. In summary, these findings testify that in endogenous genes, folding energy affects translation efficiency in a global manner that is not related to the expression levels of individual genes, and thus cannot be detected by correlation with their expression levels.

544 citations

Journal ArticleDOI
09 Jul 2009-Nature
TL;DR: It is shown that anticipation is an adaptive trait, because pre-exposure to the stimulus that typically appears early in the ecology improves the organism’s fitness when encountered with a second stimulus, and indicates that environmental anticipation may be ubiquitous in biology.
Abstract: Natural habitats of some microorganisms may fluctuate erratically, whereas others, which are more predictable, offer the opportunity to prepare in advance for the next environmental change. In analogy to classical Pavlovian conditioning, microorganisms may have evolved to anticipate environmental stimuli by adapting to their temporal order of appearance. Here we present evidence for environmental change anticipation in two model microorganisms, Escherichia coli and Saccharomyces cerevisiae. We show that anticipation is an adaptive trait, because pre-exposure to the stimulus that typically appears early in the ecology improves the organism's fitness when encountered with a second stimulus. Additionally, we observe loss of the conditioned response in E. coli strains that were repeatedly exposed in a laboratory evolution experiment only to the first stimulus. Focusing on the molecular level reveals that the natural temporal order of stimuli is embedded in the wiring of the regulatory network-early stimuli pre-induce genes that would be needed for later ones, yet later stimuli only induce genes needed to cope with them. Our work indicates that environmental anticipation is an adaptive trait that was repeatedly selected for during evolution and thus may be ubiquitous in biology.

502 citations

Journal ArticleDOI
TL;DR: An intricate association between competition and cooperation is charted indicating that the cooperative potential is maximized at moderate levels of resource overlap, which is important for the future design of consortia optimized towards bioremediation and bio-production applications.
Abstract: Revealing the ecological principles that shape communities is a major challenge of the post-genomic era. To date, a systematic approach for describing inter-species interactions has been lacking. Here we independently predict the competitive and cooperative potential between 6,903 bacterial pairs derived from a collection of 118 species' metabolic models. We chart an intricate association between competition and cooperation indicating that the cooperative potential is maximized at moderate levels of resource overlap. Utilizing ecological data from 2,801 samples, we explore the associations between bacterial interactions and coexistence patterns. The high level of competition observed between species with mutual-exclusive distribution patterns supports the role of competition in community assembly. Cooperative interactions are typically unidirectional with no obvious benefit to the giver. However, within their natural communities, bacteria typically form close cooperative loops resulting in indirect benefit to all species involved. These findings are important for the future design of consortia optimized towards bioremediation and bio-production applications.

412 citations

Journal ArticleDOI
TL;DR: Yeast cells arrested at the G1 phase of the cell cycle restrict homologous recombination, but are able to repair the DSB by NHEJ, and it is demonstrated that recombination ability does not require duplicated chromatids or passage through S phase, and is controlled at the resection step by Clb–CDK activity.
Abstract: DNA double-strand breaks (DSBs) are dangerous lesions that can lead to genomic instability and cell death. Eukaryotic cells repair DSBs either by nonhomologous end-joining (NHEJ) or by homologous recombination. We investigated the ability of yeast cells (Saccharomyces cerevisiae) to repair a single, chromosomal DSB by recombination at different stages of the cell cycle. We show that cells arrested at the G1 phase of the cell cycle restrict homologous recombination, but are able to repair the DSB by NHEJ. Furthermore, we demonstrate that recombination ability does not require duplicated chromatids or passage through S phase, and is controlled at the resection step by Clb–CDK activity.

399 citations


Cited by
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Journal ArticleDOI
13 Sep 2012-Nature
TL;DR: Viewing the microbiota from an ecological perspective could provide insight into how to promote health by targeting this microbial community in clinical treatments.
Abstract: Trillions of microbes inhabit the human intestine, forming a complex ecological community that influences normal physiology and susceptibility to disease through its collective metabolic activities and host interactions. Understanding the factors that underlie changes in the composition and function of the gut microbiota will aid in the design of therapies that target it. This goal is formidable. The gut microbiota is immensely diverse, varies between individuals and can fluctuate over time — especially during disease and early development. Viewing the microbiota from an ecological perspective could provide insight into how to promote health by targeting this microbial community in clinical treatments.

3,890 citations

Journal ArticleDOI

3,734 citations

Book ChapterDOI
31 Jan 1963

2,885 citations

Journal ArticleDOI
02 Jan 2014-Nature
TL;DR: It is shown that m6A is selectively recognized by the human YTH domain family 2 (YTHDF2) ‘reader’ protein to regulate mRNA degradation and established the role of YTH DF2 in RNA metabolism, showing that binding of Y THDF2 results in the localization of bound mRNA from the translatable pool to mRNA decay sites, such as processing bodies.
Abstract: N(6)-methyladenosine (m(6)A) is the most prevalent internal (non-cap) modification present in the messenger RNA of all higher eukaryotes. Although essential to cell viability and development, the exact role of m(6)A modification remains to be determined. The recent discovery of two m(6)A demethylases in mammalian cells highlighted the importance of m(6)A in basic biological functions and disease. Here we show that m(6)A is selectively recognized by the human YTH domain family 2 (YTHDF2) 'reader' protein to regulate mRNA degradation. We identified over 3,000 cellular RNA targets of YTHDF2, most of which are mRNAs, but which also include non-coding RNAs, with a conserved core motif of G(m(6)A)C. We further establish the role of YTHDF2 in RNA metabolism, showing that binding of YTHDF2 results in the localization of bound mRNA from the translatable pool to mRNA decay sites, such as processing bodies. The carboxy-terminal domain of YTHDF2 selectively binds to m(6)A-containing mRNA, whereas the amino-terminal domain is responsible for the localization of the YTHDF2-mRNA complex to cellular RNA decay sites. Our results indicate that the dynamic m(6)A modification is recognized by selectively binding proteins to affect the translation status and lifetime of mRNA.

2,699 citations

Journal ArticleDOI
TL;DR: This Review describes how metagenomics and 16S pyrosequencing techniques are opening the way towards global ecosystem network prediction and the development of ecosystem-wide dynamic models.
Abstract: Metagenomics and 16S pyrosequencing have enabled the study of ecosystem structure and dynamics to great depth and accuracy. Co-occurrence and correlation patterns found in these data sets are increasingly used for the prediction of species interactions in environments ranging from the oceans to the human microbiome. In addition, parallelized co-culture assays and combinatorial labelling experiments allow high-throughput discovery of cooperative and competitive relationships between species. In this Review, we describe how these techniques are opening the way towards global ecosystem network prediction and the development of ecosystem-wide dynamic models.

2,401 citations