| dc.identifier.uri | http://hdl.handle.net/11401/77613 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | Proper functioning of a multi-cellular organism requires well-coordinated intra- and inter-cellular communication among its cells. Mammalian cells have well established modes of inter-cellular communication, which include cell-cell contact via gap junctions, synaptic transmission, and paracrine and endocrine communication through secreted molecules. Extracellular vesicles (EV) serve as a vehicle for transfer of biomolecules between cells. This study aims to establish if EV mediated transfer of encapsulated RNA represents a novel mode of inter-cellular communication. At the outset, we developed and validated a novel and efficient approach of isolation of EVs. Comprehensive characterization of EV RNA derived from several cell types revealed the diversity of small RNA cargo, and suggested non-random and cell type specific sorting of RNA molecules into EVs. Further analysis revealed gene family specific fragmentation patterns of non-coding RNAs detected within EVs. Next, we explored the temporal dynamics, spatial localization, and integrity of EV RNA upon transfer into another cell. We further demonstrated cell state dependent dynamicity of EV RNA cargo, as well as cell type specific molecular responses, when different cells were exposed to the same EV stimuli, underscoring the context dependent interpretation of the complex EV messages. Finally, as a specific example of EV RNA functionality, we reported the possible involvement of a 31 nucleotide processed fragment of RNY5, one of the most abundant and enriched RNA components of cancer cell derived EVs, in selectively inducing cell death in primary cells of diverse developmental origins and identified an eight nucleotide motif crucial for its functionality. The transfer of processed, functional RNY5 fragments through EVs hints at the under-appreciated role of EV RNA in cancer cell microenvironment. Thus, our study supports the hypothesis that EV mediated transfer of RNA represents a novel mode of inter-cellular communication, through which cells may shape the transcriptional landscape of another cell in their microenvironment. | |
| dcterms.available | 2017-09-20T16:53:01Z | |
| dcterms.contributor | Jackson, David | en_US |
| dcterms.contributor | Gingeras, Thomas R. | en_US |
| dcterms.contributor | VanAelst, Linda | en_US |
| dcterms.contributor | Thomsen, Gerald | en_US |
| dcterms.contributor | Taylor, Douglas. | en_US |
| dcterms.creator | Chakrabortty, Sudipto Kumar | |
| dcterms.dateAccepted | 2017-09-20T16:53:01Z | |
| dcterms.dateSubmitted | 2017-09-20T16:53:01Z | |
| dcterms.description | Department of Genetics. | en_US |
| dcterms.extent | 182 pg. | en_US |
| dcterms.format | Application/PDF | en_US |
| dcterms.format | Monograph | |
| dcterms.identifier | http://hdl.handle.net/11401/77613 | |
| dcterms.issued | 2015-05-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:53:01Z (GMT). No. of bitstreams: 1
Chakrabortty_grad.sunysb_0771E_12531.pdf: 9766216 bytes, checksum: c764d348834e6bdd7c79343a6fb9d935 (MD5)
Previous issue date: 2015 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Genetics | |
| dcterms.subject | Exosomes, Extracellular vesicles, Genomics, Inter-cellular communication, Non-coding RNA, RNA-Seq | |
| dcterms.title | Intercellular transfer of functional RNA through extracellular vesicles is a medium of communication between cells | |
| dcterms.type | Dissertation | |
