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We began analyzing https://www.nature.com/articles/s41586-021-04234-3, but it redirected us to https://www.nature.com/articles/s41586-021-04234-3. The analysis below is for the second page.

Title[redir]:
MicroRNA sequence codes for small extracellular vesicle release and cellular retention | Nature
Description:
Exosomes and other small extracellular vesicles (sEVs) provide a unique mode of cell-to-cell communication in which microRNAs (miRNAs) produced and released from one cell are taken up by cells at a distance where they can enact changes in gene expression1–3. However, the mechanism by which miRNAs are sorted into exosomes/sEVs or retained in cells remains largely unknown. Here we demonstrate that miRNAs possess sorting sequences that determine their secretion in sEVs (EXOmotifs) or cellular retention (CELLmotifs) and that different cell types, including white and brown adipocytes, endothelium, liver and muscle, make preferential use of specific sorting sequences, thus defining the sEV miRNA profile of that cell type. Insertion or deletion of these CELLmotifs or EXOmotifs in a miRNA increases or decreases retention in the cell of production or secretion into exosomes/sEVs. Two RNA-binding proteins, Alyref and Fus, are involved in the export of miRNAs carrying one of the strongest EXOmotifs, CGGGAG. Increased miRNA delivery mediated by EXOmotifs leads to enhanced inhibition of target genes in distant cells. Thus, this miRNA code not only provides important insights that link circulating exosomal miRNAs to tissues of origin, but also provides an approach for improved targeting in RNA-mediated therapies. MicroRNAs encode sorting sequences that determine whether they are secreted in exosomal vesicles to regulate gene expression in distant cells or retained in cells that produced them, with different sequences used by individual cell types.

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Keywords {🔍}

cell, mirna, article, sev, mirnas, google, scholar, data, expression, cells, type, table, shown, cas, supplementary, enrichment, nature, normalized, extended, extracellular, cellular, average, types, fig, nucleotides, information, mirp, sequence, profile, motifs, blue, number, showing, red, wildtype, vesicles, gene, access, rna, aml, content, analysis, microrna, sample, expressed, research, versus, hepatocytes, strand, structure,

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nature portfolio journals permissions reprints nature portfolio privacy policy extracellular vesicle research c57bl/6j wild-type mice advertising mimic mir-34c wild-type oe-mir-34c-5p-wt mir-34c-5p wild-type social media author information authors oe-mir-34c-5p-cgggag mir-26a-5p wild-type ovarian research skeletal muscle development ultracentrifugation + size-exclusion chromatography experiment small extracellular vesicles nature+ nature 542 nature 601 nature mir-34c wild-type wild-type mir-34c microrna-mediated gene silencing author correspondence cell-derived sev mir-431-5p wild-type mir-677-5p wild-type wild-type mir-677-5p quantitative rt–pcr assays bone development designed research wild-type mir-140-3p mir-140-3p wild-type bonferroni post-hoc test tata-box binding protein mutant versions mir-34-ugugu sev-sec enriched-mirnas compared small rna sequencing rna-binding protein syncrip sandip kumar patel cell communication cell-type-specific mirnas research permissions exosome/sev-specific mirnas springerlink instant access cell-enriched mirnas divided article garcia-martin

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      description:ExosomesÂ and otherÂ small extracellular vesicles (sEVs) provide a unique mode of cell-to-cell communication in which microRNAs (miRNAs) produced and released from one cell are taken up by cells at a distance where they can enact changes in gene expression1â3. However, the mechanism by which miRNAs are sorted into exosomes/sEVs or retained in cells remains largely unknown. Here we demonstrate that miRNAs possess sorting sequences that determine their secretion in sEVs (EXOmotifs) or cellular retention (CELLmotifs) and that different cell types, including white and brown adipocytes, endothelium, liver and muscle, make preferential use of specific sorting sequences, thus defining the sEV miRNA profile of that cell type. Insertion or deletion of these CELLmotifs or EXOmotifs in a miRNA increases or decreases retention in the cell of production or secretion into exosomes/sEVs. Two RNA-binding proteins, Alyref and Fus, are involved in the export of miRNAs carrying one of the strongest EXOmotifs, CGGGAG. Increased miRNA delivery mediated by EXOmotifs leads to enhanced inhibition of target genes in distant cells. Thus, this miRNA code not only provides important insights that link circulating exosomal miRNAs to tissues of origin, but also provides an approach for improved targeting in RNA-mediated therapies. MicroRNAs encode sorting sequences that determine whether they are secreted in exosomal vesicles to regulate gene expression in distant cells or retained in cells that produced them, with different sequences used by individual cell types.
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