Publications by authors named "Macrae I"

Small interfering RNAs (siRNAs) guide mRNA cleavage by human Argonaute2 (hAgo2), leading to targeted gene silencing. Despite their laboratory and clinical impact, structural insights into human siRNA catalytic activity remain elusive. Here, we show that disrupting siRNA 3'-end binding by hAgo2 accelerates target cleavage and stabilizes its catalytic conformation, enabling detailed structural analysis.

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Co-transcriptional assembly is an integral feature of the formation of RNA-protein complexes that mediate translation. For ribosome synthesis, prior studies have indicated that the strict order of transcription of rRNA domains may not be obligatory during bacterial ribosome biogenesis, since a series of circularly permuted rRNAs are viable. In this work, we report the structural insights into assembly of the bacterial ribosome large subunit (LSU) based on cryo-EM density maps of intermediates that accumulate during in vitro ribosome synthesis using a set of circularly permuted (CiPer) rRNAs.

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Article Synopsis
  • Argonaute proteins play essential roles in RNA silencing, helping regulate gene expression and defend against viruses and transposons in eukaryotes, with two main types: AGOs for miRNA/siRNA and PIWIs for piRNA.
  • Research shows that a specific Argonaute protein, HrAgo1, from the Lokiarchaeon 'Candidatus Harpocratesius repetitus,' shares a common ancestry with eukaryotic PIWI proteins and is capable of RNA-guided RNA cleavage.
  • The study suggests that HrAgo1 retains ancient structural features, hinting at how Argonaute proteins might have evolved and diverged in the early stages of eukaryotic development.
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Co-transcriptional assembly is an integral feature of the formation of RNA-protein complexes that mediate translation. For ribosome synthesis, prior studies have indicated that the strict order of transcription of rRNA domains may not be obligatory during bacterial ribosome biogenesis, since a series of circularly permuted rRNAs are viable. In this work, we report the insights into assembly of the bacterial ribosome large subunit (LSU) based on cryo-EM density maps of intermediates that accumulate during ribosome synthesis using a set of circularly permuted (CiPer) rRNAs.

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Background And Aims: Developing novel therapies to battle the global public health burden of heart failure remains challenging. This study investigates the underlying mechanisms and potential treatment for 4-hydroxynonenal (4-HNE) deleterious effects in heart failure.

Methods: Biochemical, functional, and histochemical measurements were applied to identify 4-HNE adducts in rat and human failing hearts.

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Unlabelled: Brain computations are dictated by the unique morphology and connectivity of neuronal subtypes, features established by closely timed developmental events. MicroRNAs (miRNAs) are critical for brain development, but current technologies lack the spatiotemporal resolution to determine how miRNAs instruct the steps leading to subtype identity. Here, we developed new tools to tackle this major gap.

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In eukaryotes, small RNA guides, such as small interfering RNAs and microRNAs, direct AGO-clade Argonaute proteins to regulate gene expression and defend the genome against external threats. Only animals make a second clade of Argonaute proteins: PIWI proteins. PIWI proteins use PIWI-interacting RNAs (piRNAs) to repress complementary transposon transcripts.

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Argonaute (AGO) proteins use small RNAs to recognize transcripts targeted for silencing in plants and animals. Many AGOs cleave target RNAs using an endoribonuclease activity termed 'slicing'. Slicing by DNA-guided prokaryotic AGOs has been studied in detail, but structural insights into RNA-guided slicing by eukaryotic AGOs are lacking.

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Argonaute (AGO) proteins use microRNAs (miRNAs) and small interfering RNAs (siRNAs) as guides to regulate gene expression in plants and animals. AGOs that use miRNAs in bilaterian animals recognize short (6-8 nt.) elements complementary to the miRNA seed region, enabling each miRNA to interact with hundreds of otherwise unrelated targets.

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Phage restriction by adenosine deaminase acting on RNA (RADAR) is a process by which bacteria may alter their own transcriptome to resist bacteriophage. In this issue of Cell, Duncan-Lowey and Tal et al. and Gao et al.

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Remote sensing has been shown to be a promising technology for the detection and monitoring of plant stresses including insect feeding. Newman, is an invasive insect species in the United States, and a pest of concern to soybean, (L.) Merr.

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Small RNAs (sRNAs), including microRNAs (miRNAs) and small interfering RNAs (siRNAs), are essential gene regulators for plant and animal development. The loading of sRNA duplexes into the proper ARGONAUTE (AGO) protein is a key step to forming a functional silencing complex. In Arabidopsis thaliana, the specific loading of miR166/165 into AGO10 (AtAGO10) is critical for the maintenance of the shoot apical meristem, the source of all shoot organs, but the mechanism by which AtAGO10 distinguishes miR166/165 from other cellular miRNAs is not known.

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Argonaute proteins use nucleic acid guides to find and bind specific DNA or RNA target sequences. Argonaute proteins have diverse biological functions and many retain their ancestral endoribonuclease activity, cleaving the phosphodiester bond between target nucleotides t10 and t11. In animals, the PIWI proteins-a specialized class of Argonaute proteins-use 21-35 nucleotide PIWI-interacting RNAs (piRNAs) to direct transposon silencing, protect the germline genome, and regulate gene expression during gametogenesis.

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Spectral remote sensing has the potential to improve scouting and management of soybean aphid (Aphis glycines Matsumura), which can cause yield losses of over 40% in the North Central Region of the United States. We used linear support vector machines (SVMs) to determine 1) whether hyperspectral samples could be classified into treat/no-treat classes based on the economic threshold (250 aphids per plant) and 2) how many wavelengths or features are needed to generate an accurate model without overfitting the data. A range of aphid infestation levels on soybean was created using caged field plots in 2013, 2014, 2017, and 2018 in Minnesota and in 2017 and 2018 in Iowa.

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microRNAs (miRNAs) form regulatory networks in metazoans. Viruses engage miRNA networks in numerous ways, with Flaviviridae members exploiting direct interactions of their RNA genomes with host miRNAs. For hepatitis C virus (HCV), binding of liver-abundant miR-122 stabilizes the viral RNA and regulates viral translation.

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PIWI proteins use PIWI-interacting RNAs (piRNAs) to identify and silence transposable elements and thereby maintain genome integrity between metazoan generations. The targeting of transposable elements by PIWI has been compared to mRNA target recognition by Argonaute proteins, which use microRNA (miRNA) guides, but the extent to which piRNAs resemble miRNAs is not known. Here we present cryo-electron microscopy structures of a PIWI-piRNA complex from the sponge Ephydatia fluviatilis with and without target RNAs, and a biochemical analysis of target recognition.

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Hepatitis C virus (HCV) is a positive-sense RNA virus that interacts with a liver-specific microRNA called miR-122. miR-122 binds to two sites in the 5' untranslated region of the viral genome and promotes HCV RNA accumulation. This interaction is important for viral RNA accumulation in cell culture, and miR-122 inhibitors have been shown to be effective at reducing viral titers in chronic HCV-infected patients.

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The current study investigates the factor structure of the Work Values Questionnaire (WVQ) which measures how important each of 44 different features of a job are to the respondent. Over 750 international working professionals, primarily from the UK, completed a survey which included the WVQ, and measures of self-perceived success. Factor analysis (both exploratory and confirmatory) was conducted to extract factors and facets.

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Beneficial insect populations and the services that they provide are in decline, largely due to agricultural land use and practices. Establishing perennial floral plantings in the unused margins of crop fields can help conserve beneficial pollinators and predators in commercial agroecosystems. We assessed the impacts of floral plantings on both pollinators and arthropod predators when established adjacent to conventionally managed commercial potato fields.

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Small interfering RNAs (siRNAs) promote RNA degradation in a variety of processes and have important clinical applications. siRNAs direct cleavage of target RNAs by guiding Argonaute2 (AGO2) to its target site. Target site accessibility is critical for AGO2-target interactions, but how target site accessibility is controlled in vivo is poorly understood.

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microRNAs (miRNAs) are crucial for posttranscriptional regulation of messenger RNAs. "Classical" miRNA targets predominantly interact with the miRNA seed sequence located near the miRNA 5' end. Interestingly, certain transcripts that exhibit extensive complementarity to the miRNAs 3' region, instead of being subjected to regulation, induce miRNA decay in a process termed target-directed miRNA degradation (TDMD).

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Soybean aphid, Aphis glycines Matsumura, remains the most economically damaging arthropod pest of soybean in the midwestern United States and southern Canada. Foliar applications of a limited number of insecticide modes of action have been the primary management tactic, and pyrethroid resistance was documented recently with full concentration-response leaf-dip and glass-vial bioassays. Full concentration-response bioassays can be cumbersome, and a more efficient assessment tool was needed.

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Soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is a common pest of soybean, Glycine max (L.) Merrill (Fabales: Fabaceae), in North America requiring frequent scouting as part of an integrated pest management plan. Current scouting methods are time consuming and provide incomplete coverage of soybean.

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Complementarity to the microRNA (miRNA) seed region has long been recognized as the primary determinant in target recognition by the Argonaute-miRNA complex. Recently, we reported that pairing to miRNA 3'-supplementary region (nucleotides 13-16) can increase target affinity by more than an order of magnitude beyond seed-pairing alone. Here, we present biochemical evidence that supplementary interactions can drive robust differential targeting between equivalently seed-matched target RNAs in vitro.

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