Reading m⁶A marks in mRNA: A potent mechanism of gene regulation in plants

Journal of Integrative Plant Biology, Год журнала: 2024, Номер 66(12), С. 2586 - 2599

Опубликована: Окт. 4, 2024

ABSTRACT Modifications to RNA have recently been recognized as a pivotal regulator of gene expression in living organisms. More than 170 chemical modifications identified RNAs, with N 6 ‐methyladenosine (m A) being the most abundant modification eukaryotic mRNAs. The addition and removal m A marks are catalyzed by methyltransferases (referred “writers”) demethylases “erasers”), respectively. In addition, mRNAs interpreted A‐binding proteins “readers”), which regulate fate mRNAs, including stability, splicing, transport, translation. Therefore, exploring mechanism underlying reader‐mediated modulation metabolism is essential for much deeper understanding epigenetic role plants. Recent discoveries improved our functions readers plant growth development, stress response, disease resistance. This review highlights latest developments reader research, emphasizing diverse RNA‐binding domains crucial function biological cellular roles response developmental environmental signals. Moreover, we propose discuss potential future research directions challenges identifying novel elucidating mechanistic

Язык: Английский

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Methyltransferase ATMETTL5 writes m⁶A on 18S ribosomal RNA to regulate translation in Arabidopsis

New Phytologist, Год журнала: 2024, Номер 244(2), С. 571 - 587

Опубликована: Авг. 26, 2024

Aberrant RNA modifications can lead to dysregulated gene expression and impeded growth in plants. Ribosomal (rRNA) constitutes a substantial portion of total RNA, while the precise functions molecular mechanisms underlying rRNA plants remain largely elusive. Here, we elucidated exclusive occurrence canonical modification N

Язык: Английский

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Interconnections between m⁶A RNA modification, RNA structure, and protein–RNA complex assembly

Life Science Alliance, Год журнала: 2023, Номер 7(1), С. e202302240 - e202302240

Опубликована: Ноя. 7, 2023

Protein-RNA complexes exist in many forms within the cell, from stable machines such as ribosome to transient assemblies like spliceosome. All protein-RNA rely on spatially and temporally coordinated interactions between specific proteins RNAs achieve a functional form. RNA folding structure are often critical for successful protein binding complex formation. modifications change chemical nature of given alter its kinetics. Both these alterations can affect how if or other interact with modified assemble into complexes. N

Язык: Английский

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U6 snRNA m6A modification is required for accurate and efficient splicing of C. elegans and human pre-mRNAs

Nucleic Acids Research, Год журнала: 2024, Номер 52(15), С. 9139 - 9160

Опубликована: Май 29, 2024

Abstract pre-mRNA splicing is a critical feature of eukaryotic gene expression. Both cis- and trans-splicing rely on accurately recognising splice site sequences by spliceosomal U snRNAs associated proteins. Spliceosomal carry multiple RNA modifications with the potential to affect different stages splicing. Here, we show that conserved U6 snRNA m6A methyltransferase METT-10 required for accurate efficient C. elegans pre-mRNAs. The absence in METTL16 humans primarily leads alternative at 5′ sites an adenosine +4 position. In addition, weak 3′ trans-splice sites. We identified significant overlap between factor SNRNP27K regulating +4A. Finally, editing endogenous +4A positions +4U restores wild-type mett-10 mutant background, supporting direct role modification recognition. conclude important

Язык: Английский

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RNA splicing: a split consensus reveals two major 5′ splice site classes

Open Biology, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 1, 2025

The established consensus sequence for human 5′ splice sites masks the presence of two major site classes defined by preferential base-pairing potentials with either U5 snRNA loop 1 or U6 ACAGA box. are separable in genome sequences, sensitized specific genotypes and associated splicing complexity. reflect commitment to usage occurring primarily during transfer snRNA. Separating into its constituents can help us understand fundamental features eukaryote architecture mechanisms inform treatment design diseases caused genetic variation affecting splicing.

Язык: Английский

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Epitranscriptome‐Mediated Regulation of Neuronal Translation

Wiley Interdisciplinary Reviews - RNA, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 1, 2025

ABSTRACT Epitranscriptomic modification of RNA is an important layer regulation for gene expression. modifications come in many flavors and generate a complex tapestry regulatory network. Here, we focus on two major modifications, one rRNA (2′O Methylation) another mRNA (N 6 ‐Methyladenosine [m A]) their impact translation. The 2′O methyl group addition the ribose sugar plays critical role folding, ribosome assembly, its interaction with binding proteins. Differential methylation these sites contributes to heterogeneity generates potential “specialized ribosomes.” Specialized ribosomes are proposed play variety roles maintaining pluripotency, lineage specification, compartmentalized activity‐mediated translation neurons. m A modification, other hand, determines stability, transport, subclasses mRNA. dynamic nature owing localization activity writers, readers, erasers makes it powerful tool spatiotemporal While substantial information has accumulated abundance functional consequences still understudied. In this article, review literature constructing body our understanding outcome general nervous system particular. We also explore possibility how may collaborate modulating provoke thought integrate functions multiple epitranscriptome modifications.

Язык: Английский

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LUC7 proteins define two major classes of 5′ splice sites in animals and plants

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 20, 2025

Mutation or deletion of the U1 snRNP-associated factor LUC7L2 is associated with myeloid neoplasms, and knockout alters cellular metabolism. Here, we show that members LUC7 protein family differentially regulate two major classes 5' splice sites (5'SS) broadly mRNA splicing in both human cell lines leukemias copy number variation. We describe distinctive 5'SS features exons impacted by three paralogs: LUC7L enhance "right-handed" stronger consensus matching on intron side near invariant /GU, while LUC7L3 enhances "left-handed" upstream /GU. validated our model sequence-specific regulation mutating swapping domains between proteins. Evolutionary analysis indicates LUC7L2/LUC7L3 subfamilies evolved before split animals plants. Analysis Arabidopsis thaliana mutants confirmed plant orthologs possess similar specificity to their counterparts, indicating proteins highly conserved.

Язык: Английский

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Prp16 enables efficient splicing of introns with diverse exonic consensus elements in the short-intron rich Cryptococcus neoformans transcriptome

RNA Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

DEAH box splicing helicase Prp16 in budding yeast governs spliceosomal remodelling from the branching conformation (C complex) to exon ligation (C* complex). In this study, we examined genome-wide functions of short intron-rich genome basidiomycete Cryptococcus neoformans. The presence multiple introns per transcript with intronic features that are more similar those higher eukaryotes makes it a promising model for studying splicing. Using promoter-shutdown conditional knockdown strain, uncovered but substrate-specific roles C. neoformans dependent on motifs I and II, which conserved activity. A small subset spliced independent activity was investigated discover exonic sequences at 5' splice site (5'SS) 3' (3'SS) stronger affinity U5 loop 1 common feature these introns. Furthermore, (60-100nts) ultrashort (<60nts) prevalent transcriptome were sensitive than longer introns, indicating is required efficient We propose snRNA-pre-mRNA interactions enable transition spliceosome first second catalytic confirmation knockdown, particularly suboptimal features. This study provides insights into fine-tuning function variations cis-element

Язык: Английский

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Ghost authors revealed: The structure and function of human N⁶‐methyladenosine RNA methyltransferases

Wiley Interdisciplinary Reviews - RNA, Год журнала: 2023, Номер 15(1)

Опубликована: Сен. 6, 2023

Abstract Despite the discovery of modified nucleic acids nearly 75 years ago, their biological functions are still being elucidated. N 6 ‐methyladenosine (m A) is most abundant modification in eukaryotic messenger RNA (mRNA) and has also been detected non‐coding RNAs, including long RNA, ribosomal small nuclear RNA. In general, m A marks can alter secondary structure initiate unique RNA–protein interactions that splicing, mRNA turnover, translation, just to name a few. Although human RNAs have known exist since 1974, structures methyltransferases responsible for writing established only recently. Thus far, there four confirmed catalyze transfer methyl group from S ‐adenosylmethionine (SAM) position adenosine, producing A: methyltransferase‐like protein (METTL) 3/METTL14 complex, METTL16, METTL5, zinc‐finger CCHC‐domain‐containing 4. Though targets, all contain Rossmann fold with conserved SAM‐binding pocket, suggesting they utilize similar catalytic mechanism transfer. For each methyltransferases, we present links disease, kinetic mechanisms, macromolecular structures. We discuss viruses parasites, assigning transcriptome specific molecules targeting enzymes hypermodified humans. Understanding critical steppingstone toward establishing epitranscriptome more broadly RNome. This article categorized under: Interactions Proteins Other Molecules > Protein‐RNA Recognition RNA‐Protein Complexes Interactions: Functional Implications

Язык: Английский

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Interplay between N-adenosine RNA methylation and mRNA splicing

Current Opinion in Genetics & Development, Год журнала: 2024, Номер 87, С. 102211 - 102211

Опубликована: Июнь 4, 2024

N

Язык: Английский

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