Cell to cell signaling via exosomes (transport of genetic material between cells via exosomes) - Identification of RNA-binding proteins in exosomes capable of interacting with different types of RNA: RBP-facilitated transport of RNAs into exosomes

SND-ID: snd1142-1. Version: 1.0. DOI: https://doi.org/10.5878/6b1e-fs87

Citation

Creator/Principal investigator(s)

Hadi Valadi - University of Gothenburg, Avdelningen för reumatologi och inflammationsforskning orcid

Research principal

University of Gothenburg - the Institute of Medicine rorId

Description

In the human body, communication between cells takes place in several different ways. Exosomes are a type of extracellular vesicles (30-200 nm in diameter) that also participate in this process. Exosomes can be released from most cell types in the body and exist naturally in different body fluids, such as blood.

In 2007, we showed for the first time that exosomes also transport RNA molecules (both coding and non-coding RNA molecules) between cells (Valadi H. et al. Nature Cell Biology. 2007). The findings describe a new type of 'cell-cell' communication by which different cells send genetic messages to each other by secreting vesicles (exosomes) containing specific RNA molecules.

Our current studies aim to (a) identify cellular actors involved in translocation (packaging) of RNA into exosomes during their biosynthesis, (b) identify the mechanism by which exosomes are taken up by recipient cells/ tissues, and (c) ) discover a method to introduce exogenous/ therapeutic RNA into exosomes, to be used for in vivo transport of therapeutic RNA to different organs.

RNA-binding proteins (RBPs) prese

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In the human body, communication between cells takes place in several different ways. Exosomes are a type of extracellular vesicles (30-200 nm in diameter) that also participate in this process. Exosomes can be released from most cell types in the body and exist naturally in different body fluids, such as blood.

In 2007, we showed for the first time that exosomes also transport RNA molecules (both coding and non-coding RNA molecules) between cells (Valadi H. et al. Nature Cell Biology. 2007). The findings describe a new type of 'cell-cell' communication by which different cells send genetic messages to each other by secreting vesicles (exosomes) containing specific RNA molecules.

Our current studies aim to (a) identify cellular actors involved in translocation (packaging) of RNA into exosomes during their biosynthesis, (b) identify the mechanism by which exosomes are taken up by recipient cells/ tissues, and (c) ) discover a method to introduce exogenous/ therapeutic RNA into exosomes, to be used for in vivo transport of therapeutic RNA to different organs.

RNA-binding proteins (RBPs) present in exosomes derived from HTB177 cells (NCI-H460 [H460] (ATCC: HTB-177) were identified as described below.

For more detailed description please see Statello L, Maugeri M, Garre E, Nawaz M, Wahlgren J, Papadimitriou A, et al. (2018) (doi: 10.1371/journal.pone.0195969. eCollection 2018). List of the identified proteins can be found in the section 'Data collection' as well as on the journal's website (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195969#sec025).

Identification of RNA binding proteins in exosomes and their parent cells:
To detect and isolate the RBPs in cells and exosomes, the biotinylated esRNAs, cellular miRNAs, and cellular mRNAs were attached to streptavidin-coated paramagnetic Dynabeads M-280 and were incubated with native protein extracts of exosomes in separate RNA species assays (total exosomal-protein extract + esRNA;, total exosomal-protein extract + cell-mRNA;, total exosomal-protein extract + cell-miRNA). The protein-RNA complexes were eluted from the beads. The 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. Samples without RNA were processed in parallel and were used as negative controls to identify proteins that bound non-specifically to the beads. Show less..

Language

Method and outcome

Unit of analysis

Population

Currently, not available

Study design

Experimental study

Preclinical study

Time period(s) investigated

2008-01-01 – Ongoing

Data format / data structure

Data collection
  • Mode of collection: Measurements and tests
  • Time period(s) for data collection: 2008
  • Source of the data: Research data
Geographic coverage

Geographic spread

Geographic location: Sweden

Administrative information

Responsible department/unit

the Institute of Medicine

Topic and keywords

Research area

Natural sciences (Standard för svensk indelning av forskningsämnen 2011)

Medical and health sciences (Standard för svensk indelning av forskningsämnen 2011)

Publications

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Maugeri M, Nawaz M, Papadimitriou A, Angerfors A, Camponeschi A, Na M, Hölttä M, Skantze P, Johansson S, Sundqvist M, Lindquist J, Kjellman T, Mårtensson IL, Jin T, Sunnerhagen P, Östman S, Lindfors L, Valadi H., Nature Communication. 2019 Sep 24;10(1):4333. https://doi.org/10.1038/s41467-019-12275-6
Link to article
DOI: https://doi.org/10.1038/s41467-019-12275-6

Statello L, Maugeri M, Garre E, Nawaz M, Wahlgren J, Papadimitriou A, et al. (2018) Identification of RNA-binding proteins in exosomes capable of interacting with different types of RNA: RBP-facilitated transport of RNAs into exosomes. PLoS ONE 13(4): e0195969. https://doi.org/10.1371/journal.pone.0195969
Link to article
DOI: https://doi.org/10.1371/journal.pone.0195969. eCollection 2018

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Published: 2020-01-31
Last updated: 2020-01-31