Enhancing climate change resilience in agricultural crops

Current Biology, Год журнала: 2023, Номер 33(23), С. R1246 - R1261

Опубликована: Дек. 1, 2023

Climate change threatens global food and nutritional security through negative effects on crop growth agricultural productivity. Many countries have adopted ambitious climate mitigation adaptation targets that will exacerbate the problem, as they require significant changes in current agri-food systems. In this review, we provide a roadmap for improved production encompasses effective transfer of knowledge into plant breeding management strategies underpin sustainable agriculture intensification resilience. We identify main problem areas highlight outstanding questions potential solutions can be applied to mitigate impacts Although translation scientific advances lags far behind technology, consider holistic approach, combining disciplines collaborative efforts, drive better connections between research, policy, needs society.

Язык: Английский

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De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome

Nature, Год журнала: 2024, Номер 632(8026), С. 832 - 840

Опубликована: Июль 11, 2024

Abstract Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily protein-coding genes 1 . Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify RNA RNU4-2 as a syndromic NDD gene. encodes U4 small nuclear (snRNA), which is critical component U4/U6.U5 tri-snRNP complex major spliceosome 2 We an 18 base pair region mapping two structural elements U4/U6 snRNA duplex (the T-loop and stem III) that severely depleted variation general population, but heterozygous variants 115 NDD. Most (77.4%) have same highly recurrent single insertion (n.64_65insT). In 54 whom it could be determined, de novo were all on maternal allele. demonstrate expressed developing human brain, contrast RNU4-1 other homologues. Using sequencing, show how 5′ splice-site use systematically disrupted variants, consistent known role this during activation. Finally, estimate explain 0.4% This work underscores importance rare will provide diagnosis thousands worldwide.

Язык: Английский

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Structures of aberrant spliceosome intermediates on their way to disassembly

Nature Structural & Molecular Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Intron removal during pre-mRNA splicing is of extraordinary complexity and its disruption causes a vast number genetic diseases in humans. While key steps the canonical spliceosome cycle have been revealed by combined structure–function analyses, structural information on an aberrant committed to premature disassembly not available. Here, we report two cryo-electron microscopy structures post-Bact intermediates from Schizosaccharomyces pombe primed for disassembly. We identify DEAH-box helicase–G-patch protein pair (Gih35–Gpl1, homologous human DHX35–GPATCH1) show how it maintains catalytic dormancy. In both structures, Gpl1 recognizes remodeled active site introduced overstabilization U5 loop I interaction with 5′ exon leading single-nucleotide insertion at splice site. Remodeling communicated surface Ntr1 complex that mediates recruited. Our data pave way targeted analysis quality control. authors provide insights into control mechanism. The Gpl1–Gih35 binds spliceosomes, blocks progression triggers discard pathway.

Язык: Английский

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Structural insights into spliceosome fidelity: DHX35–GPATCH1- mediated rejection of aberrant splicing substrates

Cell Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 28, 2025

Abstract The spliceosome, a highly dynamic macromolecular assembly, catalyzes the precise removal of introns from pre-mRNAs. Recent studies have provided comprehensive structural insights into step-wise catalytic splicing and final disassembly spliceosome. However, molecular details how spliceosome recognizes rejects suboptimal substrates remained unclear. Here, we show cryo-electron microscopy structures spliceosomal quality control complexes thermophilic eukaryote, Chaetomium thermophilum . spliceosomes, henceforth termed B* Q , are stalled at catalytically activated state but prior to first reaction due an aberrant 5’ splice site conformation. This is recognized by G-patch protein GPATCH1, which docked onto PRP8-EN -RH domains has recruited cognate DHX35 helicase its U2 snRNA substrate. In dissociated U2/branch helix, while DHX15 close U6 RNA 3’-end Our work thus provides mechanistic concerted action two helicases in maintaining fidelity priming spliceosomes that bound for disassembly.

Язык: Английский

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Charting the epitranscriptomic landscape across RNA biotypes using native RNA nanopore sequencing

Molecular Cell, Год журнала: 2025, Номер 85(2), С. 276 - 289

Опубликована: Янв. 1, 2025

Язык: Английский

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FIONA1-mediated methylation of the 3’UTR of FLC affects FLC transcript levels and flowering in Arabidopsis

PLoS Genetics, Год журнала: 2022, Номер 18(9), С. e1010386 - e1010386

Опубликована: Сен. 27, 2022

Adenosine bases of RNA can be transiently modified by the deposition a methyl-group to form N 6 -methyladenosine (m A). This adenosine-methylation is an ancient process and enzymes involved are evolutionary highly conserved. A genetic screen designed identify suppressors late flowering transgenic Arabidopsis plants overexpressing miP1a microProtein yielded new allele FIONA1 (FIO1) m A-methyltransferase. To characterize early phenotype fio1 mutant we employed integrative approach mRNA-seq, Nanopore direct RNA-sequencing meRIP-seq differentially expressed transcripts as well methylated RNAs. We provide evidence that FIO1 elusive methyltransferase responsible for 3’-end methylation FLOWERING LOCUS C ( FLC ) transcript. Furthermore, our biochemical data suggest 3’-methylation stabilizes mRNAs non-methylated target rapid degradation.

Язык: Английский

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FLK is an mRNA m6A reader that regulates floral transition by modulating the stability and splicing of FLC in Arabidopsis

Molecular Plant, Год журнала: 2023, Номер 16(5), С. 919 - 929

Опубликована: Апрель 12, 2023

Язык: Английский

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RNA methylation in plants: An overview

Frontiers in Plant Science, Год журнала: 2023, Номер 14

Опубликована: Март 1, 2023

RNA methylation is an important post-transcriptional modification that influences gene regulation. Over 200 different types of modifications have been identified in plants. In animals, the mystery has revealed, and its biological role applications become increasingly clear. However, plants still poorly understood. Recently, plant science research on advanced rapidly, it clear plays a critical development. This review summarizes current knowledge Plant writers, erasers, readers are highlighted, as well occurrence, methods, software development summarized. The most common abundant N6-methyladenosine (m 6 A). Arabidopsis, mutations affected plant’s phenotype. It also demonstrated methylated TRANSLATIONALLY CONTROLLED TUMOR PROTEIN 1-messenger moves from shoot to root while unmethylated TCTP1-mRNA does not. Methylated immunoprecipitation, conjunction with next-generation sequencing, watershed moment research. method used successfully rice, Brassica, maize study transcriptome-wide methylation. Various or tools detect RNAs at whole transcriptome level; majority model-based analysis (for example, MACS2). Finally, limitations future prospects documented.

Язык: Английский

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N 2-methylguanosine modifications on human tRNAs and snRNA U6 are important for cell proliferation, protein translation and pre-mRNA splicing

Nucleic Acids Research, Год журнала: 2023, Номер 51(14), С. 7496 - 7519

Опубликована: Июнь 7, 2023

Abstract Modified nucleotides in non-coding RNAs, such as tRNAs and snRNAs, represent an important layer of gene expression regulation through their ability to fine-tune mRNA maturation translation. Dysregulation modifications the enzymes installing them have been linked various human pathologies including neurodevelopmental disorders cancers. Several methyltransferases (MTases) are regulated allosterically by TRMT112 (Trm112 Saccharomyces cerevisiae), but interactome this regulator targets its interacting MTases remain incompletely characterized. Here, we investigated interaction network intact cells identify three poorly characterized putative (TRMT11, THUMPD3 THUMPD2) direct partners. We demonstrate that these proteins active N2-methylguanosine (m2G) TRMT11 methylate positions 10 6 tRNAs, respectively. For THUMPD2, discovered it directly associates with U6 snRNA, a core component catalytic spliceosome, is required for formation m2G, last ‘orphan’ modification snRNA. Furthermore, our data reveal combined importance optimal protein synthesis cell proliferation well role THUMPD2 fine-tuning pre-mRNA splicing.

Язык: Английский

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Understanding the dynamic design of the spliceosome

Trends in Biochemical Sciences, Год журнала: 2024, Номер 49(7), С. 583 - 595

Опубликована: Апрель 18, 2024

Язык: Английский

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