The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Distinct mechanisms of microRNA sorting into cancer cell-derived extracellular vesicle subtypes
Published version of a preprint
Abstract
Extracellular vesicles (EVs) encompass a variety of vesicles secreted into the extracellular space. EVs have been implicated in promoting tumor metastasis, but the molecular composition of tumor-derived EV sub-types and the mechanisms by which molecules are sorted into EVs remain mostly unknown. We report the separation of two small EV sub-populations from a metastatic breast cancer cell line, with biochemical features consistent with different sub-cellular origins. These EV sub-types use different mechanisms of miRNA sorting (selective and non-selective), suggesting that sorting occurs via fundamentally distinct processes, possibly dependent on EV origin. Using biochemical and genetic tools, we identified the Lupus La protein as mediating sorting of selectively packaged miRNAs. We found that two motifs embedded in miR-122 are responsible for high-affinity binding to Lupus La and sorting into vesicles formed in a cell-free reaction. Thus, tumor cells can simultaneously deploy multiple EV species using distinct sorting mechanisms that may enable diverse functions in normal and cancer biology.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Several RNA-binding proteins have been identified to be associated with selective packaging of miR-122, including lupus La protein [63] and human ELAV protein HuR under stress, both verified in human cell lines [64].”
From Differential RNA packaging into small extracellular vesicles by neurons and astrocytes (2021) · cites this paper as [63]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Cutadapt removes adapter sequences from high-throughput sequencing reads
Martin, M. (2011) · EMBnet.journal · doi:10.14806/ej.17.1.200 · Cited by 33,889
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437
Extracellular vesicles: Exosomes, microvesicles, and friends
Raposo, G., & Stoorvogel, W. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201211138 · Cited by 8,099
REVIGO summarizes and visualizes long lists of gene ontology terms
Supek, F., Bošnjak, M., Škunca, N., & Šmuc, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021800 · Cited by 6,264
DNA targeting specificity of RNA-guided Cas9 nucleases
Hsu, P. D., Scott, D. A., Weinstein, J. A., Ran, F. A., Konermann, S., Agarwala, V., Li, Y., Fine, E. J., Wu, X., Shalem, O., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2647 · Cited by 4,741
CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes
Gilbert, L. A., Larson, M. H., Morsut, L., Liu, Z., Brar, G. A., Torres, S. E., Stern-Ginossar, N., Brandman, O., Whitehead, E. H., Doudna, J. A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.044 · Cited by 3,696 · cited 3×
“To test the relevance of the three RBPs in miR-122 packaging into sEVs, we used CRISPR interference (CRISPRi) ( Gilbert et al., 2013 ; Horlbeck et al., 2016 ) to systematically knock down each protein in MDA-MB-231 cells.”
MethodKowal, J., Arras, G., Colombo, M., Jouve, M., Morath, J. P., Primdal-Bengtson, B., Dingli, F., Loew, D., Tkach, M., & Théry, C. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521230113 · Cited by 3,426
Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation
Gilbert, L. A., Horlbeck, M. A., Adamson, B., Villalta, J. E., Chen, Y., Whitehead, E. H., Guimaraes, C., Panning, B., Ploegh, H. L., Bassik, M. C., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.029 · Cited by 2,728
A unifying model for mTORC1-mediated regulation of mRNA translation
Thoreen, C. C., Chantranupong, L., Keys, H. R., Wang, T., Gray, N. S., & Sabatini, D. M. (2012) · Nature · doi:10.1038/nature11083 · Cited by 1,477
Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis
Zhou, W., Fong, M. Y., Min, Y., Somlo, G., Liu, L., Palomares, M. R., Yu, Y., Chow, A., O’Connor, S. T. F., Chin, A. R., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.03.007 · Cited by 1,476
Flagged first, then by citations
Research works printed but not linked: 76
- Admyre, 2007, Exosomes with immune modulatory features are present in human breast milk, The Journal of Immunology, 179, 1969, 10.4049/jimmunol.179.3.1969 · DOI
- Al-Ejeh, 2007, The La autoantigen is a Malignancy-Associated cell death target that is induced by DNA-Damaging drugs, Clinical Cancer Research, 13, 5509, 10.1158/1078-0432.CCR-07-0922 · DOI
- Baglio, 2016, Sensing of latent EBV infection through exosomal transfer of 5'pppRNA, PNAS, 113, E587, 10.1073/pnas.1518130113 · DOI
- Bailey, 1994, Fitting a mixture model by expectation maximization to discover motifs in biopolymers, Proceedings. International Conference on Intelligent Systems for Molecular Biology, 2, 28
- Bartel, 2004, MicroRNAs: genomics, biogenesis, mechanism, and function, Cell, 116, 281, 10.1016/s0092-8674(04)00045-5 · DOI
- Bobrie, 2012, Diverse subpopulations of vesicles secreted by different intracellular mechanisms are present in exosome preparations obtained by differential ultracentrifugation, Journal of Extracellular Vesicles, 1, 18397, 10.3402/jev.v1i0.18397 · DOI
- Boyle, 2004, GO::TermFinder--open source software for accessing gene ontology information and finding significantly enriched gene ontology terms associated with a list of genes, Bioinformatics, 20, 3710, 10.1093/bioinformatics/bth456 · DOI · Paper page
- Caby, 2005, Exosomal-like vesicles are present in human blood plasma, International Immunology, 17, 879, 10.1093/intimm/dxh267 · DOI
- Cardinali, 2003, La protein is associated with terminal oligopyrimidine mRNAs in actively translating polysomes, Journal of Biological Chemistry, 278, 35145, 10.1074/jbc.M300722200 · DOI
- Cha, 2015, KRAS-dependent sorting of miRNA to exosomes, eLife, 4, 10.7554/eLife.07197 · DOI
- Cocucci, 2009, Shedding microvesicles: artefacts no more, Trends in Cell Biology, 19, 43, 10.1016/j.tcb.2008.11.003 · DOI · Paper page
- Colombo, 2014, Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles, Annual Review of Cell and Developmental Biology, 30, 255, 10.1146/annurev-cellbio-101512-122326 · DOI · Paper page
- Coulouarn, 2009, Loss of miR-122 expression in liver Cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties, Oncogene, 28, 3526, 10.1038/onc.2009.211 · DOI
- Crosio, 2000, La protein has a positive effect on the translation of TOP mRNAs in vivo, Nucleic Acids Research, 28, 2927, 10.1093/nar/28.15.2927 · DOI
- Demory Beckler, 2013, Proteomic Analysis of Exosomes from Mutant KRAS Colon Cancer Cells Identifies Intercellular Transfer of Mutant KRAS, Molecular & Cellular Proteomics, 12, 343, 10.1074/mcp.M112.022806 · DOI
- Dickman, 2017, Selective extracellular vesicle exclusion of miR-142-3p by oral Cancer cells promotes both internal and extracellular malignant phenotypes, Oncotarget, 8, 15252, 10.18632/oncotarget.14862 · DOI
- Feist, 2015, Proteomic challenges: sample preparation techniques for microgram-quantity protein analysis from biological samples, International Journal of Molecular Sciences, 16, 3537, 10.3390/ijms16023537 · DOI
- Flores, 2014, Differential RISC association of endogenous human microRNAs predicts their inhibitory potential, Nucleic Acids Research, 42, 4629, 10.1093/nar/gkt1393 · DOI
- Gibbings, 2009, Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity, Nature Cell Biology, 11, 1143, 10.1038/ncb1929 · DOI
- Gorur, 2017, COPII-coated membranes function as transport carriers of intracellular procollagen I, The Journal of Cell Biology, 216, 1745, 10.1083/jcb.201702135 · DOI
- Gould, 2019, 'A shared pathway of exosome biogenesis operates at plasma and endosome membranes', 10.1101/545228 · DOI
- Harding, 1983, Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes, The Journal of Cell Biology, 97, 329, 10.1083/jcb.97.2.329 · DOI · Paper page
- Horlbeck, 2016, Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation, eLife, 5, 10.7554/eLife.19760 · DOI · Paper page
- Hsu, 2010, Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C, The Journal of Cell Biology, 189, 223, 10.1083/jcb.200911018 · DOI
- Hsu, 2017, Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1, Oncogene, 36, 4929, 10.1038/onc.2017.105 · DOI
- Intine, 2003, Differential phosphorylation and subcellular localization of La RNPs associated with precursor tRNAs and translation-related mRNAs, Molecular Cell, 12, 1301, 10.1016/S1097-2765(03)00429-5 · DOI
- Jeppesen, 2019, Reassessment of exosome composition, Cell, 177, 428, 10.1016/j.cell.2019.02.029 · DOI · Paper page
- Kim, 2015, HISAT: a fast spliced aligner with low memory requirements, Nature Methods, 12, 357, 10.1038/nmeth.3317 · DOI · Paper page
- Koppers-Lalic, 2014, Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes, Cell Reports, 8, 1649, 10.1016/j.celrep.2014.08.027 · DOI · Paper page
- Langmead, 2012, Fast gapped-read alignment with bowtie 2, Nature Methods, 9, 357, 10.1038/nmeth.1923 · DOI · Paper page
- Li, 2009, The sequence alignment/Map format and SAMtools, Bioinformatics, 25, 2078, 10.1093/bioinformatics/btp352 · DOI · Paper page
- Liang, 2013, Characterization and proteomic analysis of ovarian cancer-derived exosomes, Journal of Proteomics, 80, 171, 10.1016/j.jprot.2012.12.029 · DOI
- Meckes, 2013, Modulation of B-cell exosome proteins by gamma herpesvirus infection, PNAS, 110, E2925, 10.1073/pnas.1303906110 · DOI
- Mittelbrunn, 2011, Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells, Nature Communications, 2, 10.1038/ncomms1285 · DOI
- Mohr, 2013, Thermostable group II intron reverse transcriptase fusion proteins and their use in cDNA synthesis and next-generation RNA sequencing, RNA, 19, 958, 10.1261/rna.039743.113 · DOI
- Montecalvo, 2012, Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes, Blood, 119, 756, 10.1182/blood-2011-02-338004 · DOI · Paper page
- Mukherjee, 2016, Reversible HuR-microRNA binding controls extracellular export of miR-122 and augments stress response, EMBO Reports, 17, 1184, 10.15252/embr.201541930 · DOI · Paper page
- Ostenfeld, 2014, Cellular disposal of miR23b by RAB27-dependent exosome release is linked to acquisition of metastatic properties, Cancer Research, 74, 5758, 10.1158/0008-5472.CAN-13-3512 · DOI
- Ostrowski, 2010, Rab27a and Rab27b control different steps of the exosome secretion pathway, Nature Cell Biology, 12, 19, 10.1038/ncb2000 · DOI
- Pan, 1985, Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes, The Journal of Cell Biology, 101, 942, 10.1083/jcb.101.3.942 · DOI
- Pegtel, 2010, Functional delivery of viral miRNAs via exosomes, PNAS, 107, 6328, 10.1073/pnas.0914843107 · DOI
- Peinado, 2017, Pre-metastatic niches: organ-specific homes for metastases, Nature Reviews Cancer, 17, 302, 10.1038/nrc.2017.6 · DOI · Paper page
- Peritz, 2006, Immunoprecipitation of mRNA-protein complexes, Nature Protocols, 1, 577, 10.1038/nprot.2006.82 · DOI
- Petz, 2012, PDGF enhances IRES-mediated translation of laminin B1 by cytoplasmic accumulation of La during epithelial to mesenchymal transition, Nucleic Acids Research, 40, 9738, 10.1093/nar/gks760 · DOI
- Petz, 2012, La enhances IRES-mediated translation of laminin B1 during malignant epithelial to mesenchymal transition, Nucleic Acids Research, 40, 290, 10.1093/nar/gkr717 · DOI
- Pisitkun, 2004, Identification and proteomic profiling of exosomes in human urine, PNAS, 101, 13368, 10.1073/pnas.0403453101 · DOI
- Qin, 2016, High-throughput sequencing of human plasma RNA by using thermostable group II intron reverse transcriptases, RNA, 22, 111, 10.1261/rna.054809.115 · DOI
- Rana, 2013, Exosomal tumor microRNA modulates premetastatic organ cells, Neoplasia, 15, 10.1593/neo.122010 · DOI
- Rinke, 1985, Association of the lupus antigen La with a subset of U6 snRNA molecules, Nucleic Acids Research, 13, 2617, 10.1093/nar/13.7.2617 · DOI
- Rio, 2014, Electrophoretic mobility shift assays for RNA-protein complexes, Cold Spring Harbor Protocols, 2014, 435, 10.1101/pdb.prot080721 · DOI
- Rodríguez, 2014, Different exosome cargo from plasma/bronchoalveolar lavage in non-small-cell lung Cancer, Genes, Chromosomes and Cancer, 22, 713, 10.1002/gcc.22181 · DOI
- Santangelo, 2016, The RNA-Binding protein SYNCRIP is a component of the hepatocyte exosomal machinery controlling MicroRNA sorting, Cell Reports, 17, 799, 10.1016/j.celrep.2016.09.031 · DOI · Paper page
- Shurtleff, 2016, Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction, eLife, 5, 10.7554/eLife.19276 · DOI · Paper page
- Shurtleff, 2017, Broad role for YBX1 in defining the small noncoding RNA composition of exosomes, PNAS, 114, E8987, 10.1073/pnas.1712108114 · DOI
- Shurtleff, 2018, Extracellular vesicles and Cancer: caveat lector, Annual Review of Cancer Biology, 2, 395, 10.1146/annurev-cancerbio-030617-050519 · DOI
- Sirkis, 2017, Neurodegeneration-associated mutant TREM2 proteins abortively cycle between the ER and ER-Golgi intermediate compartment, Molecular Biology of the Cell, 28, 2723, 10.1091/mbc.e17-06-0423 · DOI
- Skottvoll, 2018, Comparison of ultracentrifugation and a commercial kit for isolation of exosomes derived from glioblastoma and breast Cancer cell lines, 10.1101/274910 · DOI
- Sommer, 2011, The RNA-binding protein La contributes to cell proliferation and CCND1 expression, Oncogene, 30, 434, 10.1038/onc.2010.425 · DOI
- Sommer, 2011, Implication of RNA-binding protein La in proliferation, migration and invasion of lymph node-metastasized hypopharyngeal SCC cells, PLOS ONE, 6, 10.1371/journal.pone.0025402 · DOI
- Squadrito, 2014, Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells, Cell Reports, 8, 1432, 10.1016/j.celrep.2014.07.035 · DOI · Paper page
- Stefano, 1984, Purified lupus antigen La recognizes an oligouridylate stretch common to the 3' termini of RNA polymerase III transcripts, Cell, 36, 145, 10.1016/0092-8674(84)90083-7 · DOI
- Swanson, 2006, Retrovirus RNA trafficking: from chromatin to invasive genomes, Traffic, 7, 1440, 10.1111/j.1600-0854.2006.00488.x · DOI
- Szczepanski, 2011, Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-beta1, Haematologica, 96, 1302, 10.3324/haematol.2010.039743 · DOI
- Tan, 2009, Expanded RNA-binding activities of mammalian argonaute 2, Nucleic Acids Research, 37, 7533, 10.1093/nar/gkp812 · DOI
- Tominaga, 2015, Brain metastatic Cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier, Nature Communications, 6, 10.1038/ncomms7716 · DOI · Paper page
- Tosar, 2015, Assessment of small RNA sorting into different extracellular fractions revealed by high-throughput sequencing of breast cell lines, Nucleic Acids Research, 43, 5601, 10.1093/nar/gkv432 · DOI · Paper page
- Trotta, 2003, BCR/ABL activates mdm2 mRNA translation via the La antigen, Cancer Cell, 3, 145, 10.1016/S1535-6108(03)00020-5 · DOI
- Van Deun, 2014, The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling, Journal of Extracellular Vesicles, 3, 24858, 10.3402/jev.v3.24858 · DOI
- van Niekerk, 2007, Sumoylation in axons triggers retrograde transport of the RNA-binding protein la, PNAS, 104, 12913, 10.1073/pnas.0611562104 · DOI
- Vella, 2007, Packaging of prions into exosomes is associated with a novel pathway of PrP processing, The Journal of Pathology, 211, 582, 10.1002/path.2145 · DOI
- Villarroya-Beltri, 2013, Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs, Nature Communications, 4, 10.1038/ncomms3980 · DOI · Paper page
- Wang, 2012, MiR-122 inhibits cell proliferation and tumorigenesis of breast Cancer by targeting IGF1R, PLOS ONE, 7, 10.1371/journal.pone.0047053 · DOI
- Wei, 2016, Fetal bovine serum RNA interferes with the cell culture derived extracellular RNA, Scientific Reports, 6, 10.1038/srep31175 · DOI
- Willms, 2016, Cells release subpopulations of exosomes with distinct molecular and biological properties, Scientific Reports, 6, 10.1038/srep22519 · DOI
- Wolin, 2002, The La protein, Annual Review of Biochemistry, 71, 375, 10.1146/annurev.biochem.71.090501.150003 · DOI
- Wu, 2012, De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast Cancer, Journal of Translational Medicine, 10, 10.1186/1479-5876-10-42 · DOI
Cited by
Sorted by citations
RNA delivery by extracellular vesicles in mammalian cells and its applications
O’Brien, K., Breyne, K., Ughetto, S., Laurent, L. C., & Breakefield, X. O. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0251-y · Cited by 1,811
Extracellular Vesicles and Nanoparticles: Emerging Complexities
Jeppesen, D. K., Zhang, Q., Franklin, J. L., & Coffey, R. J. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.01.002 · Cited by 705
Regulation of exosome production and cargo sorting
Wei, H., Chen, Q., Lin, L., Sha, C., Li, T., Liu, Y., Yin, X., Xu, Y., Chen, L., Gao, W., et al. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.53671 · Cited by 385
Current Knowledge on Exosome Biogenesis, Cargo-Sorting Mechanism and Therapeutic Implications
Xie, S., Zhang, Q., & Jiang, L. (2022) · Membranes · doi:10.3390/membranes12050498 · Cited by 262
Differential RNA packaging into small extracellular vesicles by neurons and astrocytes
Luo, X., Jean-Toussaint, R., Sacan, A., & Ajit, S. K. (2021) · Cell Communication and Signaling · doi:10.1186/s12964-021-00757-4 · Cited by 32
Metadata
- Authors
- Temoche-Diaz, M. M., Shurtleff, M. J., Nottingham, R. M., Yao, J., Fadadu, R. P., Lambowitz, A. M., & Schekman, R.
- Affiliations
- Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, United States
- Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas, Austin, United States
- Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2019-08-22
- Volume
- 8
- ISSN
- 2050-084X
- PMC
- PMC6728143
- Cited by
- 227
- References
- 12
- Language
- en
- Licence
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (R01 GM37949)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review