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Ocean acidification does not impair the behaviour of coral reef fishes 期刊论文
NATURE, 2020, 577 (7790) : 370-+
作者:  Clark, Timothy D.;  Raby, Graham D.;  Roche, Dominique G.;  Binning, Sandra A.;  Speers-Roesch, Ben;  Jutfelt, Fredrik;  Sundin, Josefin
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/03

The partial pressure of CO2 in the oceans has increased rapidly over the past century, driving ocean acidification and raising concern for the stability of marine ecosystems(1-3). Coral reef fishes are predicted to be especially susceptible to end-of-century ocean acidification on the basis of several high-profile papers(4,5) that have reported profound behavioural and sensory impairments-for example, complete attraction to the chemical cues of predators under conditions of ocean acidification. Here, we comprehensively and transparently show that-in contrast to previous studies-end-of-century ocean acidification levels have negligible effects on important behaviours of coral reef fishes, such as the avoidance of chemical cues from predators, fish activity levels and behavioural lateralization (left-right turning preference). Using data simulations, we additionally show that the large effect sizes and small within-group variances that have been reported in several previous studies are highly improbable. Together, our findings indicate that the reported effects of ocean acidification on the behaviour of coral reef fishes are not reproducible, suggesting that behavioural perturbations will not be a major consequence for coral reef fishes in high CO2 oceans.


  
Analyses of non-coding somatic drivers in 2,658 cancer whole genomes 期刊论文
NATURE, 2020, 578 (7793) : 102-+
作者:  Clark, Timothy D.;  Raby, Graham D.;  Roche, Dominique G.;  Binning, Sandra A.;  Speers-Roesch, Ben;  Jutfelt, Fredrik;  Sundin, Josefin
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

The discovery of drivers of cancer has traditionally focused on protein-coding genes(1-4). Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium(5) of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers(6,7), raise doubts about others and identify novel candidates, including point mutations in the 5'  region of TP53, in the 3'  untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.


  
Zucchini consensus motifs determine the mechanism of pre-piRNA production 期刊论文
NATURE, 2020, 578 (7794) : 311-+
作者:  Clark, Timothy D.;  Raby, Graham D.;  Roche, Dominique G.;  Binning, Sandra A.;  Speers-Roesch, Ben;  Jutfelt, Fredrik;  Sundin, Josefin
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

PIWI-interacting RNAs (piRNAs) of between approximately 24 and 31 nucleotides in length guide PIWI proteins to silence transposons in animal gonads, thereby ensuring fertility(1). In the biogenesis of piRNAs, PIWI proteins are first loaded with 5 '  -monophosphorylated RNA fragments called pre-pre-piRNAs, which then undergo endonucleolytic cleavage to produce pre-piRNAs(1,2). Subsequently, the 3 '  -ends of pre-piRNAs are trimmed by the exonuclease Trimmer (PNLDC1 in mouse)(3-6) and 2 '  -O-methylated by the methyltransferase Hen1 (HENMT1 in mouse)(7-9), generating mature piRNAs. It is assumed that the endonuclease Zucchini (MitoPLD in mouse) is a major enzyme catalysing the cleavage of pre-pre-piRNAs into pre-piRNAs(10-13). However, direct evidence for this model is lacking, and how pre-piRNAs are generated remains unclear. Here, to analyse pre-piRNA production, we established a Trimmer-knockout silkworm cell line and derived a cell-free system that faithfully recapitulates Zucchini-mediated cleavage of PIWI-loaded pre-pre-piRNAs. We found that pre-piRNAs are generated by parallel Zucchini-dependent and -independent mechanisms. Cleavage by Zucchini occurs at previously unrecognized consensus motifs on pre-pre-piRNAs, requires the RNA helicase Armitage, and is accompanied by 2 '  -O-methylation of pre-piRNAs. By contrast, slicing of pre-pre-piRNAs with weak Zucchini motifs is achieved by downstream complementary piRNAs, producing pre-piRNAs without 2 '  -O-methylation. Regardless of the endonucleolytic mechanism, pre-piRNAs are matured by Trimmer and Hen1. Our findings highlight multiplexed processing of piRNA precursors that supports robust and flexible piRNA biogenesis.


A silkworm model recapitulates key steps of Zucchini-mediated cleavage of pre-pre-piRNA and provides insights into Zucchini-mediated and -independent pathways that generate pre-piRNAs, which converge to a common piRNA maturation step.