CoChat
Sign Up
Cited by 242

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

Identification of RNA-binding proteins in exosomes capable of interacting with different types of RNA: RBP-facilitated transport of RNAs into exosomes

Statello, Luisa, Maugeri, Marco, Garre, Elena, Nawaz, Muhammad, Wahlgren, Jessica, Papadimitriou, Alexandros, Lundqvist, Christina, Lindfors, Lennart, Collén, Anna, Sunnerhagen, Per, Ragusa, Marco, Purrello, Michele, Di Pietro, Cinzia, Tigue, Natalie, Valadi, Hadi·2018·PLOS ONE
DOI 10.1371/journal.pone.0195969PMC PMC5918169
Open this paper in CoChat — free account

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0195969

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Figures

Fig 1 (A) RNA 3’-end labelling of cellular (miRNA, mRNA) and exosomal-RNAs (esRNA). The dot blot shows the efficiency of biotinylation of cellular miRNAs and mRNA, and exosomal total RNA (esRNA), relative to the biotinylated IRE control. A 43 nucleotide synthetic RNA template was used as a positive control for the reaction and as a general mass control. Serial dilutions of the labelled samples were loaded onto a nylon membrane, UV cross-linked, and detected by chemiluminescence. Dot blots show the efficiency of the RNA labelling reaction and the amount of the biotinylated RNA obtained. The biotinylation reaction for all RNA species esRNA, cell-miRNA and cell-mRNA was highly efficient, with biotinylation rates greater than 75%. (B) RNA electrophoretic mobility shift sssays (REMSAs) of cellular and exosomal RNA-RBP-complexes: Total exosomal-RNA (esRNA), cell-miRNA and cell-mRNA fractions extracted from HTB (lung) cells were incubated in binding reactions with exosomal proteins and with HTB cellular proteins. In all experiments, an electrophoretic shift was observed when the biotinylated RNA was incubated with the proteins from exosomes and cells. The specificities of the RNA-protein interactions were determined using competition assays. From left to right: the interaction of IRE RNA and cytosolic liver extract (positive control), the interaction of IRE RNA with cellular proteins, the interaction of cellular miRNAs with cellular proteins, the interaction of esRNA with exosomal proteins, and the interaction of cellular miRNA with exosomal proteins. The band-shifts are indicated by squares.
Fig 1 (A) RNA 3’-end labelling of cellular (miRNA, mRNA) and exosomal-RNAs (esRNA). The dot blot shows the efficiency of biotinylation of cellular miRNAs and mRNA, and exosomal total RNA (esRNA), relative to the biotinylated IRE control. A 43 nucleotide synthetic RNA template was used as a positive control for the reaction and as a general mass control. Serial dilutions of the labelled samples were loaded onto a nylon membrane, UV cross-linked, and detected by chemiluminescence. Dot blots show the efficiency of the RNA labelling reaction and the amount of the biotinylated RNA obtained. The biotinylation reaction for all RNA species esRNA, cell-miRNA and cell-mRNA was highly efficient, with biotinylation rates greater than 75%. (B) RNA electrophoretic mobility shift sssays (REMSAs) of cellular and exosomal RNA-RBP-complexes: Total exosomal-RNA (esRNA), cell-miRNA and cell-mRNA fractions extracted from HTB (lung) cells were incubated in binding reactions with exosomal proteins and with HTB cellular proteins. In all experiments, an electrophoretic shift was observed when the biotinylated RNA was incubated with the proteins from exosomes and cells. The specificities of the RNA-protein interactions were determined using competition assays. From left to right: the interaction of IRE RNA and cytosolic liver extract (positive control), the interaction of IRE RNA with cellular proteins, the interaction of cellular miRNAs with cellular proteins, the interaction of esRNA with exosomal proteins, and the interaction of cellular miRNA with exosomal proteins. The band-shifts are indicated by squares.CC BY · PubMed Central
Fig 2 Identification of RNA-binding proteins (RBPs) from exosomes and their interactions with different RNA species. Total exosomal proteins were isolated and incubated separately in independent assays; (total exosomal protein extract + esRNA; total exosomal protein extract + cell-mRNA; total exosomal protein extract + cell-miRNA) and their interaction with RNA species were identified. From total exosomal proteins, 30 were identified as RNA-binding proteins (i.e. exosomal-RBPs). (A) Schematic representation of biotinylation, streptavidin and LC-MS/MS experimental procedures used to label RNA, and to identify exosomal-RBPs respectively. (i) Total RNA isolated from exosomes, and cells from independent assays was biotinylated and streptavidin-coated Dynabeads were added. (ii) The isolated native total exosomal proteins were incubated separately with esRNA, cell-mRNA and cell-miRNA, and allowed to bind with biotinylated RNAs in separate reactions. (iii) Proteins were re-extracted and RBPs bound to the different RNAs were then loaded onto an SDS-PAGE gel, and target bands were excised, trypsinised and analyzed using LC-MS/MS. (B) List of the identified exosomal-RBPs from independent assays, which interact with cellular RNA and esRNA from different assays. (C) Venn diagrams displaying the overlap of 30 RBPs identified in exosomal-associated with exosomal RNA (esRNA), cellular mRNAs, and cellular miRNAs. In total, 30 different RBPs were identified in exosomes, including 20 in complex with esRNA. Out of 20 esRNA-binding exosomal-RBPs, the 12 exosomal-RBPs were exclusive to esRNA, 2 were common between the esRNA and cell-mRNA samples, 2 were common between the esRNA and cell-miRNA samples and 4 RBPs were common in all three samples i.e. esRNA, cell-mRNA and cell-miRNA. 9 exosomal-RBPs in complex with cell-miRNA, 14 in complex with cell-mRNA and 1 was common between cell-miRNA and cell-mRNA samples. 2 exosomal-RBPs were in complex with cell-miRNA only, and 7 were in complex with cell-mRNA only.
Fig 2 Identification of RNA-binding proteins (RBPs) from exosomes and their interactions with different RNA species. Total exosomal proteins were isolated and incubated separately in independent assays; (total exosomal protein extract + esRNA; total exosomal protein extract + cell-mRNA; total exosomal protein extract + cell-miRNA) and their interaction with RNA species were identified. From total exosomal proteins, 30 were identified as RNA-binding proteins (i.e. exosomal-RBPs). (A) Schematic representation of biotinylation, streptavidin and LC-MS/MS experimental procedures used to label RNA, and to identify exosomal-RBPs respectively. (i) Total RNA isolated from exosomes, and cells from independent assays was biotinylated and streptavidin-coated Dynabeads were added. (ii) The isolated native total exosomal proteins were incubated separately with esRNA, cell-mRNA and cell-miRNA, and allowed to bind with biotinylated RNAs in separate reactions. (iii) Proteins were re-extracted and RBPs bound to the different RNAs were then loaded onto an SDS-PAGE gel, and target bands were excised, trypsinised and analyzed using LC-MS/MS. (B) List of the identified exosomal-RBPs from independent assays, which interact with cellular RNA and esRNA from different assays. (C) Venn diagrams displaying the overlap of 30 RBPs identified in exosomal-associated with exosomal RNA (esRNA), cellular mRNAs, and cellular miRNAs. In total, 30 different RBPs were identified in exosomes, including 20 in complex with esRNA. Out of 20 esRNA-binding exosomal-RBPs, the 12 exosomal-RBPs were exclusive to esRNA, 2 were common between the esRNA and cell-mRNA samples, 2 were common between the esRNA and cell-miRNA samples and 4 RBPs were common in all three samples i.e. esRNA, cell-mRNA and cell-miRNA. 9 exosomal-RBPs in complex with cell-miRNA, 14 in complex with cell-mRNA and 1 was common between cell-miRNA and cell-mRNA samples. 2 exosomal-RBPs were in complex with cell-miRNA only, and 7 were in complex with cell-mRNA only.CC BY · PubMed Central
Fig 3 Network analysis of all (30) identified RBPs in exosomes. The key function of the identified RBPs was retrieved using Ingenuity software (www.ingenuity.com) to build a biological network of the RBPs in exosomes. The network included 35 nodes (gene products), 27 of which were among the identified exosomal-RBPs including MVP (indicated in grey). The network shows the involvement of exosomal-RBPs in ‘RNA posttranscriptional modifications’.
Fig 3 Network analysis of all (30) identified RBPs in exosomes. The key function of the identified RBPs was retrieved using Ingenuity software (www.ingenuity.com) to build a biological network of the RBPs in exosomes. The network included 35 nodes (gene products), 27 of which were among the identified exosomal-RBPs including MVP (indicated in grey). The network shows the involvement of exosomal-RBPs in ‘RNA posttranscriptional modifications’.CC BY · PubMed Central
Fig 4 The gene transcripts encoding six RBPs identified in exosomes were silenced in the cytoplasm by siRNA and the subsequent effect on the amount of esRNA was assessed. A significant reduction of total RNA in exosomes (esRNA) was shown by post-transcriptional silencing of MVP. (A) Confirmation of gene silencing (silenced transcripts) in the cells after transfection with the siRNAs against the transcripts of HSP90AB1, XPO5, hnRNPH1, hnRNPM, hnRNPA2B1, and MVP with respect to the Negative Control siRNA (scrambled siRNA). Quantitative PCR was performed using cDNA, Fast SYBR Green Master Mix, and gene-specific primers. Gene expression was normalized to that of the housekeeping gene GAPDH. The error bars represent average of 4 biological replicates for hnRNPA2B1 and MVP, and 2 biological replicates for other four transcripts, and the average fold change values presented as RQ (relative quantification). (B) Quantification (the percentage-change, %) of total RNA present in exosomes (ng total esRNA / μg total exosomal proteins) after each gene silencing, i.e. silencing of HSP90AB1, XPO5, hnRNPH1, hnRNPM, and hnRNPA2B1. The silencing of hnRNPA2B1 caused a slight reduction of total RNA present in exosomes, but at non-significant level ≈13%. However, after silencing of hnRNPH1 the amount of RNA in exosomes was increased as compared to negative control. The experiment was performed in duplicates, except from hnRNPA2B1 that was performed in 4 replicates. The graph shows the range of values and median (grey). (C-D) Quantification of total RNA (ng total RNA / μg total protein) present in cells and exosomes after gene silencing of MVP. (C) A slight increase (but not significant, p-value 0.57) of the amount of total RNA in cytoplasm was observed. (D) On the contrary, down regulation of MVP (silencing) caused a significant reduction of the total RNA present in exosomes (esRNA), approximately by 50% (p-value 0.02). The experiment for MVP silencing was performed in four replicates; the graph shows the range of values and median (grey).
Fig 4 The gene transcripts encoding six RBPs identified in exosomes were silenced in the cytoplasm by siRNA and the subsequent effect on the amount of esRNA was assessed. A significant reduction of total RNA in exosomes (esRNA) was shown by post-transcriptional silencing of MVP. (A) Confirmation of gene silencing (silenced transcripts) in the cells after transfection with the siRNAs against the transcripts of HSP90AB1, XPO5, hnRNPH1, hnRNPM, hnRNPA2B1, and MVP with respect to the Negative Control siRNA (scrambled siRNA). Quantitative PCR was performed using cDNA, Fast SYBR Green Master Mix, and gene-specific primers. Gene expression was normalized to that of the housekeeping gene GAPDH. The error bars represent average of 4 biological replicates for hnRNPA2B1 and MVP, and 2 biological replicates for other four transcripts, and the average fold change values presented as RQ (relative quantification). (B) Quantification (the percentage-change, %) of total RNA present in exosomes (ng total esRNA / μg total exosomal proteins) after each gene silencing, i.e. silencing of HSP90AB1, XPO5, hnRNPH1, hnRNPM, and hnRNPA2B1. The silencing of hnRNPA2B1 caused a slight reduction of total RNA present in exosomes, but at non-significant level ≈13%. However, after silencing of hnRNPH1 the amount of RNA in exosomes was increased as compared to negative control. The experiment was performed in duplicates, except from hnRNPA2B1 that was performed in 4 replicates. The graph shows the range of values and median (grey). (C-D) Quantification of total RNA (ng total RNA / μg total protein) present in cells and exosomes after gene silencing of MVP. (C) A slight increase (but not significant, p-value 0.57) of the amount of total RNA in cytoplasm was observed. (D) On the contrary, down regulation of MVP (silencing) caused a significant reduction of the total RNA present in exosomes (esRNA), approximately by 50% (p-value 0.02). The experiment for MVP silencing was performed in four replicates; the graph shows the range of values and median (grey).CC BY · PubMed Central
Fig 5 Validation of MVP. Transfected cells are expressing MVP-biotin and un-transfected cells were used as negative control. (A) Western blot analysis for the detection of MVP in HEK293F cell lysate and exosomal protein extracts shows that plasmid (MVP-biotin) was successfully expressed in HEK293F cells and was partitioned into exosomes isolated from these transfected cells. (B) Protein samples from different stages of MVP purification were separated by SDS-PAGE and the protein bands were detected by Comassie staining. After the pull down assay, the presence of MVP within exosomes was confirmed, i.e. MVP in exosomes from biotinylated MVP-transfected cells PD (pull-down lane), whereas it was absent in exosomes from untransfected cells. The position of the MVP-biotin band is indicated by squares. A representative experiment out of 3 is shown. (C) Total amount of RNAs coupled to MVP were extracted and quantified by Quant-iT™ RiboGreen® RNA Assay Kit (ThermoFisher Scientific). Captured RNA was expressed as a percentage of RNA eluted from the beads after the pull-down respect to the total RNA incubated with the beads. Exosomal-MVP was coupled with RNAs and the quantification of RNAs that had co-eluted with MVP showed that the amount of RNA present in the MVP elute (i.e. from MVP-RNA complex) was significantly higher than that from the untransfected control. The experiment was performed in 3-replicates and the graph shows the range of values and median (grey). Average and standard error of three independent experiments are shown. Samples: W = proteins from different wash steps during the MVP purification, and PD = pull-down proteins (MVP) after elution, I = input, and UB = unbound after RBP capture.
Fig 5 Validation of MVP. Transfected cells are expressing MVP-biotin and un-transfected cells were used as negative control. (A) Western blot analysis for the detection of MVP in HEK293F cell lysate and exosomal protein extracts shows that plasmid (MVP-biotin) was successfully expressed in HEK293F cells and was partitioned into exosomes isolated from these transfected cells. (B) Protein samples from different stages of MVP purification were separated by SDS-PAGE and the protein bands were detected by Comassie staining. After the pull down assay, the presence of MVP within exosomes was confirmed, i.e. MVP in exosomes from biotinylated MVP-transfected cells PD (pull-down lane), whereas it was absent in exosomes from untransfected cells. The position of the MVP-biotin band is indicated by squares. A representative experiment out of 3 is shown. (C) Total amount of RNAs coupled to MVP were extracted and quantified by Quant-iT™ RiboGreen® RNA Assay Kit (ThermoFisher Scientific). Captured RNA was expressed as a percentage of RNA eluted from the beads after the pull-down respect to the total RNA incubated with the beads. Exosomal-MVP was coupled with RNAs and the quantification of RNAs that had co-eluted with MVP showed that the amount of RNA present in the MVP elute (i.e. from MVP-RNA complex) was significantly higher than that from the untransfected control. The experiment was performed in 3-replicates and the graph shows the range of values and median (grey). Average and standard error of three independent experiments are shown. Samples: W = proteins from different wash steps during the MVP purification, and PD = pull-down proteins (MVP) after elution, I = input, and UB = unbound after RBP capture.CC BY · PubMed Central
Fig 6 Two hypothetical paths (A and B) for the packaging of RNA–protein–complexes (RNPs) into exosomes during biosynthesis of these vesicles from the multivesicular bodies (MVBs): (A) The RNP-granules i.e. RNA–protein complexes to be included into exosomes (so called esRNA-protein complex) use a budding mechanism to enter into intraluminal vesicles of MVBs as RNA-protein granules. In doing so, first, they form an intermediate vesicle inside the MVBs, by inward budding–a mechanism similar to nuclear envelop (NE) budding as shown by [90–92]. The intermediate vesicles are matured and transformed into intraluminal vesicles inside MVB. Upon fusion of MVB with the plasma membrane, the intraluminal vesicles (exosomes) will be released outside containing RNA-RNPs complexes into the extracellular environment. In the second model (B) RNA–protein complexes (RNPs)—transported via nuclear pore complex (NPC)—are attracted to the internalization site having different receptor-proteins that could mediate inward budding of MVBs, to form intraluminal vesicles. Upon fusion with the plasma membrane, the MVBs release the intraluminal vesicles (exosomes) containing RNA–RNPs complexes into the extracellular environment.
Fig 6 Two hypothetical paths (A and B) for the packaging of RNA–protein–complexes (RNPs) into exosomes during biosynthesis of these vesicles from the multivesicular bodies (MVBs): (A) The RNP-granules i.e. RNA–protein complexes to be included into exosomes (so called esRNA-protein complex) use a budding mechanism to enter into intraluminal vesicles of MVBs as RNA-protein granules. In doing so, first, they form an intermediate vesicle inside the MVBs, by inward budding–a mechanism similar to nuclear envelop (NE) budding as shown by [90–92]. The intermediate vesicles are matured and transformed into intraluminal vesicles inside MVB. Upon fusion of MVB with the plasma membrane, the intraluminal vesicles (exosomes) will be released outside containing RNA-RNPs complexes into the extracellular environment. In the second model (B) RNA–protein complexes (RNPs)—transported via nuclear pore complex (NPC)—are attracted to the internalization site having different receptor-proteins that could mediate inward budding of MVBs, to form intraluminal vesicles. Upon fusion with the plasma membrane, the MVBs release the intraluminal vesicles (exosomes) containing RNA–RNPs complexes into the extracellular environment.CC BY · PubMed Central

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.

A few free checks a day · papers already verified open instantly · results are public

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?

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

Show all 7 references

Research works printed but not linked: 85

  1. B Fevrier, 2004, Exosomes: endosomal-derived vesicles shipping extracellular messages, Current opinion in cell biology, 16, 415, 10.1016/j.ceb.2004.06.003 · DOI · Paper page
  2. M Nawaz, 2014, The emerging role of extracellular vesicles as biomarkers for urogenital cancers, Nature reviews Urology, 11, 688, 10.1038/nrurol.2014.301 · DOI
  3. F Fatima, 2017, Vesiculated Long Non-Coding RNAs: Offshore Packages Deciphering Trans-Regulation between Cells, Cancer Progression and Resistance to Therapies, Non-Coding RNA, 3, 10, 10.3390/ncrna3010010 · DOI
  4. S Mathivanan, 2010, Exosomes: extracellular organelles important in intercellular communication, Journal of proteomics, 73, 1907, 10.1016/j.jprot.2010.06.006 · DOI
  5. M Nawaz, 2017, Extracellular Vesicles, Tunneling Nanotubes, and Cellular Interplay: Synergies and Missing Links, Front Mol Biosci, 4, 50, 10.3389/fmolb.2017.00050 · DOI
  6. M Simons, 2009, Exosomes—vesicular carriers for intercellular communication, Current opinion in cell biology, 21, 575, 10.1016/j.ceb.2009.03.007 · DOI
  7. AK Ludwig, 2012, Exosomes: small vesicles participating in intercellular communication, The international journal of biochemistry & cell biology, 44, 11, 10.1016/j.biocel.2011.10.005 · DOI
  8. F Fatima, 2017, Long Distance Metabolic Regulation through Adipose-Derived Circulating Exosomal miRNAs: A Trail for RNA-Based Therapies?, Front Physiol, 8, 545, 10.3389/fphys.2017.00545 · DOI
  9. M Yanez-Mo, 2015, Biological properties of extracellular vesicles and their physiological functions, J Extracell Vesicles, 4, 27066, 10.3402/jev.v4.27066 · DOI · Paper page
  10. T Katsuda, 2013, The roles of extracellular vesicles in cancer biology: towards the development of novel cancer biomarkers, Proteomics
  11. SA Bellingham, 2012, Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases?, Frontiers in physiology, 3, 124, 10.3389/fphys.2012.00124 · DOI · Paper page
  12. EI Buzas, 2014, Emerging role of extracellular vesicles in inflammatory diseases, Nature reviews Rheumatology, 10, 356, 10.1038/nrrheum.2014.19 · DOI
  13. MI Ramirez, 2018, Technical challenges of working with extracellular vesicles, Nanoscale
  14. DJ Gibbings, 2009, Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity, Nat Cell Biol, 11, 1143, 10.1038/ncb1929 · DOI
  15. C Lasser, 2011, Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages, J Transl Med, 9, 9, 10.1186/1479-5876-9-9 · DOI · Paper page
  16. SS Luo, 2009, Human villous trophoblasts express and secrete placenta-specific microRNAs into maternal circulation via exosomes, Biol Reprod, 81, 717, 10.1095/biolreprod.108.075481 · DOI · Paper page
  17. A Michael, 2009, Exosomes from human saliva as a source of microRNA biomarkers, Oral Dis, 16, 34, 10.1111/j.1601-0825.2009.01604.x · DOI
  18. KC Miranda, 2010, Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease, Kidney Int, 78, 191, 10.1038/ki.2010.106 · DOI
  19. J Skog, 2008, Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers, Nat Cell Biol, 10, 1470, 10.1038/ncb1800 · DOI · Paper page
  20. J Wahlgren, 2012, Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes, Nucleic Acids Res, 40, e130, 10.1093/nar/gks463 · DOI
  21. M Kanada, 2015, Differential fates of biomolecules delivered to target cells via extracellular vesicles, Proceedings of the National Academy of Sciences of the United States of America, 112, E1433, 10.1073/pnas.1418401112 · DOI
  22. DM Pegtel, 2010, Functional delivery of viral miRNAs via exosomes, Proceedings of the National Academy of Sciences of the United States of America, 107, 6328, 10.1073/pnas.0914843107 · DOI
  23. B Mateescu, 2017, Obstacles and opportunities in the functional analysis of extracellular vesicle RNA—an ISEV position paper, J Extracell Vesicles, 6, 1286095, 10.1080/20013078.2017.1286095 · DOI
  24. M Eldh, 2010, Exosomes communicate protective messages during oxidative stress; possible role of exosomal shuttle RNA, PLoS One, 5, e15353, 10.1371/journal.pone.0015353 · DOI
  25. SA Bellingham, 2012, Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells, Nucleic Acids Res
  26. A 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
  27. M Ragusa, 2014, Highly skewed distribution of miRNAs and proteins between colorectal cancer cells and their exosomes following Cetuximab treatment: biomolecular, genetic and translational implications, Oncoscience, 1, 132, 10.18632/oncoscience.19 · DOI
  28. MJ 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
  29. T Glisovic, 2008, RNA-binding proteins and post-transcriptional gene regulation, FEBS Lett, 582, 1977, 10.1016/j.febslet.2008.03.004 · DOI · Paper page
  30. S Gerstberger, 2014, A census of human RNA-binding proteins, Nature reviews Genetics, 15, 829, 10.1038/nrg3813 · DOI · Paper page
  31. J Ratajczak, 2006, Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery, Leukemia, 20, 847, 10.1038/sj.leu.2404132 · DOI
  32. JD Arroyo, 2011, Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma, Proceedings of the National Academy of Sciences of the United States of America, 108, 5003, 10.1073/pnas.1019055108 · DOI · Paper page
  33. A Turchinovich, 2011, Characterization of extracellular circulating microRNA, Nucleic acids research, 39, 7223, 10.1093/nar/gkr254 · DOI · Paper page
  34. C Gourzones, 2013, Consistent high concentration of the viral microRNA BART17 in plasma samples from nasopharyngeal carcinoma patients—evidence of non-exosomal transport, Virology journal, 10, 119, 10.1186/1743-422X-10-119 · DOI
  35. JG Patton, 2015, Biogenesis, delivery, and function of extracellular RNA, Journal of extracellular vesicles, 4, 27494, 10.3402/jev.v4.27494 · DOI
  36. J Guduric-Fuchs, 2012, Selective extracellular vesicle-mediated export of an overlapping set of microRNAs from multiple cell types, BMC genomics, 13, 357, 10.1186/1471-2164-13-357 · DOI
  37. JR Chevillet, 2014, Quantitative and stoichiometric analysis of the microRNA content of exosomes, Proceedings of the National Academy of Sciences of the United States of America, 111, 14888, 10.1073/pnas.1408301111 · DOI
  38. C Villarroya-Beltri, 2013, Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs, Nature communications, 4, 2980, 10.1038/ncomms3980 · DOI · Paper page
  39. L 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
  40. MF Bolukbasi, 2012, miR-1289 and "Zipcode"-like Sequence Enrich mRNAs in Microvesicles, Mol Ther Nucleic Acids, 1, e10, 10.1038/mtna.2011.2 · DOI
  41. AJ McKenzie, 2016, KRAS-MEK Signaling Controls Ago2 Sorting into Exosomes, Cell reports, 15, 978, 10.1016/j.celrep.2016.03.085 · DOI
  42. ML Squadrito, 2014, Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells, Cell Rep, 8, 1432, 10.1016/j.celrep.2014.07.035 · DOI · Paper page
  43. BW van Balkom, 2015, Quantitative and qualitative analysis of small RNAs in human endothelial cells and exosomes provides insights into localized RNA processing, degradation and sorting, J Extracell Vesicles, 4, 26760, 10.3402/jev.v4.26760 · DOI
  44. JP Tosar, 2015, Assessment of small RNA sorting into different extracellular fractions revealed by high-throughput sequencing of breast cell lines, Nucleic Acids Res, 43, 5601, 10.1093/nar/gkv432 · DOI · Paper page
  45. A Iavello, 2016, Role of Alix in miRNA packaging during extracellular vesicle biogenesis, International journal of molecular medicine, 37, 958, 10.3892/ijmm.2016.2488 · DOI · Paper page
  46. A Marchler-Bauer, 2011, CDD: a Conserved Domain Database for the functional annotation of proteins, Nucleic Acids Res, 39, D225, 10.1093/nar/gkq1189 · DOI
  47. T Kampers, 1996, RNA stimulates aggregation of microtubule-associated protein tau into Alzheimer-like paired helical filaments, FEBS Lett, 399, 344, 10.1016/S0014-5793(96)01386-5 · DOI · Paper page
  48. D Koppers-Lalic, 2014, Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes, Cell Rep, 8, 1649, 10.1016/j.celrep.2014.08.027 · DOI · Paper page
  49. M Gonzalez-Begne, 2009, Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT), J Proteome Res, 8, 1304, 10.1021/pr800658c · DOI
  50. S Mathivanan, 2010, Proteomics analysis of A33 immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature, Mol Cell Proteomics, 9, 197, 10.1074/mcp.M900152-MCP200 · DOI
  51. C Olver, 2007, Proteomic analysis of secreted exosomes, Subcell Biochem, 43, 99, 10.1007/978-1-4020-5943-8_7 · DOI
  52. S Mathivanan, 2012, ExoCarta 2012: database of exosomal proteins, RNA and lipids, Nucleic Acids Res, 40, D1241, 10.1093/nar/gkr828 · DOI
  53. S Principe, 2013, In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine, Proteomics, 13, 1667, 10.1002/pmic.201200561 · DOI
  54. JL Welton, 2016, Proteomics analysis of vesicles isolated from plasma and urine of prostate cancer patients using a multiplex, aptamer-based protein array, J Extracell Vesicles, 5, 31209, 10.3402/jev.v5.31209 · DOI
  55. S Keerthikumar, 2016, ExoCarta: A Web-Based Compendium of Exosomal Cargo, Journal of molecular biology, 428, 688, 10.1016/j.jmb.2015.09.019 · DOI
  56. G Dreyfuss, 2002, Messenger-RNA-binding proteins and the messages they carry, Nat Rev Mol Cell Biol, 3, 195, 10.1038/nrm760 · DOI
  57. K Bomsztyk, 1997, Diverse molecular interactions of the hnRNP K protein, FEBS Lett, 403, 113, 10.1016/S0014-5793(97)00041-0 · DOI
  58. A Chaudhury, 2010, Heterogeneous nuclear ribonucleoproteins (hnRNPs) in cellular processes: Focus on hnRNP E1's multifunctional regulatory roles, RNA, 16, 1449, 10.1261/rna.2254110 · DOI
  59. AB Shyu, 2000, The double lives of shuttling mRNA binding proteins, Cell, 102, 135, 10.1016/S0092-8674(00)00018-0 · DOI
  60. N Volk, 2011, Versatility of MicroRNA biogenesis, PLoS One, 6, e19391, 10.1371/journal.pone.0019391 · DOI
  61. YS Lee, 2009, Silencing by small RNAs is linked to endosomal trafficking, Nat Cell Biol, 11, 1150, 10.1038/ncb1930 · DOI
  62. S Jha, 2009, RVB1/RVB2: running rings around molecular biology, Mol Cell, 34, 521, 10.1016/j.molcel.2009.05.016 · DOI
  63. SG Park, 2005, Functional expansion of aminoacyl-tRNA synthetases and their interacting factors: new perspectives on housekeepers, Trends Biochem Sci, 30, 569, 10.1016/j.tibs.2005.08.004 · DOI
  64. GS Hussey, 2011, Identification of an mRNP complex regulating tumorigenesis at the translational elongation step, Mol Cell, 41, 419, 10.1016/j.molcel.2011.02.003 · DOI
  65. D Haussecker, 2010, Human tRNA-derived small RNAs in the global regulation of RNA silencing, RNA, 16, 673, 10.1261/rna.2000810 · DOI
  66. EN Nolte-'t Hoen, 2012, Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions, Nucleic Acids Res
  67. G Jannot, 2011, The ribosomal protein RACK1 is required for microRNA function in both C. elegans and humans, EMBO Rep, 12, 581, 10.1038/embor.2011.66 · DOI
  68. M van Kouwenhove, 2011, MicroRNA regulation by RNA-binding proteins and its implications for cancer, Nat Rev Cancer, 11, 644, 10.1038/nrc3107 · DOI · Paper page
  69. S Iwasaki, 2010, Hsc70/Hsp90 chaperone machinery mediates ATP-dependent RISC loading of small RNA duplexes, Mol Cell, 39, 292, 10.1016/j.molcel.2010.05.015 · DOI
  70. D Koppers-Lalic, 2014, Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes, Cell Rep, 8, 1649, 10.1016/j.celrep.2014.08.027 · DOI · Paper page
  71. S Wani, 2018, Cancer cells govern miR-2909 exosomal recruitment through its 3'-end post-transcriptional modification, Cell Biochem Funct, 36, 106, 10.1002/cbf.3323 · DOI
  72. J Li, 2016, Identification and Characterization of 293T Cell-Derived Exosomes by Profiling the Protein, mRNA and MicroRNA Components, PLoS One, 11, e0163043, 10.1371/journal.pone.0163043 · DOI
  73. SA Melo, 2014, Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis, Cancer Cell, 26, 707, 10.1016/j.ccell.2014.09.005 · DOI
  74. VN Kim, 2006, Genomics of microRNA, Trends in Genetics, 22, 165, 10.1016/j.tig.2006.01.003 · DOI
  75. P Bouvet, 2001, Recognition of pre-formed and flexible elements of an RNA stem-loop by nucleolin, J Mol Biol, 309, 763, 10.1006/jmbi.2001.4691 · DOI
  76. M Srivastava, 1999, Molecular dissection of nucleolin's role in growth and cell proliferation: new insights, FASEB J, 13, 1911, 10.1096/fasebj.13.14.1911 · DOI
  77. K Tominaga, 2011, Competitive regulation of nucleolin expression by HuR and miR-494, Mol Cell Biol, 31, 4219, 10.1128/MCB.05955-11 · DOI
  78. C Yang, 2002, Identification of nucleolin and nucleophosmin as genotoxic stress-responsive RNA-binding proteins, Nucleic Acids Res, 30, 2251, 10.1093/nar/30.10.2251 · DOI
  79. P Folk, 2004, Transcriptional coregulator SNW/SKIP: the concealed tie of dissimilar pathways, Cell Mol Life Sci, 61, 629, 10.1007/s00018-003-3215-4 · DOI
  80. EN Nolte-'t Hoen, 2012, Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions, Nucleic acids research, 40, 9272, 10.1093/nar/gks658 · DOI
  81. F Fatima, 2017, Non-coding RNAs in Mesenchymal Stem Cell-Derived Extracellular Vesicles: Deciphering Regulatory Roles in Stem Cell Potency, Inflammatory Resolve, and Tissue Regeneration, Front Genet, 8, 161, 10.3389/fgene.2017.00161 · DOI
  82. Y Teng, 2017, MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression, Nature communications, 8, 14448, 10.1038/ncomms14448 · DOI · Paper page
  83. SD Speese, 2012, Nuclear Envelope Budding Enables Large Ribonucleoprotein Particle Export during Synaptic Wnt Signaling (vol 149, pg 832, 2012), Cell, 151, 687, 10.1016/j.cell.2012.10.003 · DOI
  84. A Parchure, 2017, Getting mRNA-Containing Ribonucleoprotein Granules Out of a Nuclear Back Door, Neuron, 96, 604, 10.1016/j.neuron.2017.10.020 · DOI
  85. B Fahrenkrog, 2003, The nuclear pore complex: nucleocytoplasmic transport and beyond, Nat Rev Mol Cell Biol, 4, 757, 10.1038/nrm1230 · DOI

Cited by

Sorted by citations

Metadata

Authors
Statello, L., Maugeri, M., Garre, E., Nawaz, M., Wahlgren, J., Papadimitriou, A., Lundqvist, C., Lindfors, L., Collén, A., Sunnerhagen, P., Ragusa, M., Purrello, M., Di Pietro, C., Tigue, N., & Valadi, H.
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2018-04-24
Volume
13
Issue
4
Pages
e0195969
ISSN
1932-6203
DOI
10.1371/journal.pone.0195969
PMC
PMC5918169
Cited by
242
References
7
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • Vetenskapsrådet
  • Stiftelsen för Strategisk Forskning (IRC15-0065)
  • Aroseniusfonden
  • Magnus Bergvalls Stiftelse
  • IngaBritt och Arne Lundbergs Forskningsstiftelse
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (12/24574-3)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (99999.007057/2015-06)

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