Long non-coding RNAs: definitions, functions, challenges and recommendations

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(6), P. 430 - 447

Published: Jan. 3, 2023

Language: Английский

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Long Noncoding RNAs: Molecular Modalities to Organismal Functions

Annual Review of Biochemistry, Journal Year: 2020, Volume and Issue: 89(1), P. 283 - 308

Published: June 20, 2020

We have known for decades that long noncoding RNAs (lncRNAs) can play essential functions across most forms of life. The maintenance chromosome length requires an lncRNA (e.g., hTERC) and two lncRNAs in the ribosome are required protein synthesis. Thus, represent powerful RNA machines. More recently, it has become clear mammalian genomes encode thousands more lncRNAs. we raise question: Which, if any, these could also RNA-based machines? Here synthesize studies beginning to address this question by investigating fundamental properties genes, revealing new insights into structure–function relationship, determining cis- trans-acting vivo, generating developments high-throughput screening used identify functional Overall, findings provide a context toward understanding molecular grammar underlying biology.

Language: Английский

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Landscape and Regulation of m6A and m6Am Methylome across Human and Mouse Tissues

Molecular Cell, Journal Year: 2019, Volume and Issue: 77(2), P. 426 - 440.e6

Published: Oct. 30, 2019

Language: Английский

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Preclinical and Clinical Development of Noncoding RNA Therapeutics for Cardiovascular Disease

Circulation Research, Journal Year: 2020, Volume and Issue: 126(5), P. 663 - 678

Published: Feb. 27, 2020

RNA modulation has become a promising therapeutic approach for the treatment of several types disease. The emerging field noncoding RNA-based therapies now come to attention cardiovascular research, in which it could provide valuable advancements comparison current pharmacotherapy such as small molecule drugs or antibodies. In this review, we focus on studies conducted mainly large-animal models, including pigs, rabbits, dogs, and nonhuman primates. obstacles promises targeting long RNAs circRNAs modalities humans are specifically discussed. We also describe novel ex vivo methods based human cells tissues, engineered heart tissues living myocardial slices that help bridging gap between models clinical applications future. Finally, summarize antisense oligonucleotide have already been approved by Food Drug Administration mRNAs discuss progress trials. Additional factors, drug chemistry, formulations, different routes administration, advantages drugs, included present review. Recently, first miRNA-based inhibitory strategies tested failure patients well healthy volunteers study effects wound healing (NCT04045405; NCT03603431). summary, combination targets, with cells/tissues, new delivery techniques will likely lead significant development next-generation therapeutics

Language: Английский

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Alternative splicing during mammalian organ development

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(6), P. 925 - 934

Published: May 3, 2021

Abstract Alternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed patterns across pre- postnatal development seven organs six mammals a bird. Our analyses revealed that developmentally dynamic events, which are especially prevalent brain, substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during show strongest signals regulated AS. Newly emerged cassette typically incorporated late testis development, but those retained evolution predominantly brain specific. work suggests an intricate interplay programs controlling gene expression levels fundamental organ for heart. In these regulatory networks, affords substantial functional diversification genes through generation tissue- time-specific isoforms from broadly expressed genes.

Language: Английский

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The molecular evolution of spermatogenesis across mammals

Nature, Journal Year: 2022, Volume and Issue: 613(7943), P. 308 - 316

Published: Dec. 21, 2022

The testis produces gametes through spermatogenesis and evolves rapidly at both the morphological molecular level in mammals1-6, probably owing to evolutionary pressure on males be reproductively successful7. However, evolution of individual spermatogenic cell types across mammals remains largely uncharacterized. Here we report analyses single-nucleus transcriptome data for testes from 11 species that cover three main mammalian lineages (eutherians, marsupials monotremes) birds (the outgroup), include seven primates. We find rapid was driven by accelerated fixation rates gene expression changes, amino acid substitutions new genes late stages, facilitated reduced pleiotropic constraints, haploid selection transcriptionally permissive chromatin. identify temporal changes conserved programs controlling ancestral processes. Genes predominantly expressed spermatogonia (germ cells fuelling spermatogenesis) Sertoli (somatic support) accumulated X chromosomes during evolution, presumably male-beneficial selective forces. Further work identified transcriptomal differences between X- Y-bearing spermatids uncovered meiotic sex-chromosome inactivation (MSCI) also occurs monotremes hence is common systems. Thus, mechanism silencing unsynapsed chromatin, which underlies MSCI, an feature. Our study illuminates associated forces, provides a resource investigating biology mammals.

Language: Английский

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Cancer-associated fibroblast-specific lncRNA LINC01614 enhances glutamine uptake in lung adenocarcinoma

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Oct. 8, 2022

Abstract Background Besides featured glucose consumption, recent studies reveal that cancer cells might prefer “addicting” specific energy substrates from the tumor microenvironment (TME); however, underlying mechanisms remain unclear. Methods Fibroblast-specific long noncoding RNAs were screened using RNA-seq data of our NJLCC cohort, TCGA, and CCLE datasets. The expression package LINC01614 into exosomes identified flow cytometric sorting, fluorescence in situ hybridization (FISH), quantitative reverse transcription polymerase chain reaction (RT-PCR). transfer functional role lung adenocarcinoma (LUAD) CAFs investigated 4-thiouracil-labeled RNA gain- loss-of-function approaches. pull-down, immunoprecipitation, dual-luciferase assay, gene microarray, bioinformatics analysis performed to investigate involved. Results We demonstrate cancer-associated fibroblasts (CAFs) LUAD primarily enhance glutamine metabolism cells. A CAF-specific RNA, LINC01614, packaged by CAF-derived exosomes, mediates enhancement uptake Mechanistically, directly interacts with ANXA2 p65 facilitate activation NF-κB, which leads upregulation transporters SLC38A2 SLC7A5 eventually enhances influx Reciprocally, tumor-derived proinflammatory cytokines upregulate CAFs, constituting a feedforward loop between Blocking exosome-transmitted inhibits addiction growth vivo. Clinically, is associated poor prognosis patients LUAD. Conclusion Our study highlights therapeutic potential targeting lncRNA inhibit utilization progression

Language: Английский

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Developmental mechanisms underlying the evolution of human cortical circuits

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(4), P. 213 - 232

Published: Feb. 15, 2023

Language: Английский

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A single-cell transcriptome atlas profiles early organogenesis in human embryos

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(4), P. 604 - 615

Published: March 16, 2023

Language: Английский

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Cellular development and evolution of the mammalian cerebellum

Nature, Journal Year: 2023, Volume and Issue: 625(7996), P. 788 - 796

Published: Nov. 29, 2023

The expansion of the neocortex, a hallmark mammalian evolution

Language: Английский

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