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Role of ribosomal RNA released from red cells in blood coagulation in zebrafish and humans
Hemolytic disorders are characterized by hemolysis and are prone to thrombosis. It has previously been shown that the RNA released from damaged blood cells activates clotting. However, the nature of the RNA released from hemolysis is still elusive. We found that after hemolysis, red blood cells from...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society of Hematology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759119/ https://www.ncbi.nlm.nih.gov/pubmed/34547768 http://dx.doi.org/10.1182/bloodadvances.2020003325 |
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author | Alharbi, Abdulmajeed Iyer, Neha Al Qaryoute, Ayah Raman, Revathi Burks, David J. Azad, Rajeev K. Jagadeeswaran, Pudur |
author_facet | Alharbi, Abdulmajeed Iyer, Neha Al Qaryoute, Ayah Raman, Revathi Burks, David J. Azad, Rajeev K. Jagadeeswaran, Pudur |
author_sort | Alharbi, Abdulmajeed |
collection | PubMed |
description | Hemolytic disorders are characterized by hemolysis and are prone to thrombosis. It has previously been shown that the RNA released from damaged blood cells activates clotting. However, the nature of the RNA released from hemolysis is still elusive. We found that after hemolysis, red blood cells from both zebrafish and humans released RNA that contained mostly 5.8S ribosomal RNA (5.8S rRNA), This RNA activated coagulation in zebrafish and human plasmas. By using both natural and synthetic 5.8S rRNA and its truncated fragments, we found that the 3'-end 26-nucleotide-long RNA (3'-26 RNA) and its stem-loop secondary structure were necessary and sufficient for clotting activity. Corn trypsin inhibitor (CTI), a coagulation factor XII (FXII) inhibitor, blocked 3'-26 RNA–mediated coagulation activation in the plasma of both zebrafish and humans. CTI also inhibited zebrafish coagulation in vivo. 5.8S rRNA monoclonal antibody inhibited both 5.8S rRNA– and 3'-26 RNA–mediated zebrafish coagulation activity. Both 5.8S rRNA and 3'-26 RNA activated normal human plasma but did not activate FXII-deficient human plasma. Taken together, these results suggested that the activation of zebrafish plasma is via an FXII-like protein. Because zebrafish have no FXII and because hepatocyte growth factor activator (Hgfac) has sequence similarities to FXII, we knocked down the hgfac in adult zebrafish. We found that plasma from this knockdown fish does not respond to 3'-26 RNA. To summarize, we identified that an rRNA released in hemolysis activates clotting in human and zebrafish plasma. Furthermore, we showed that fish Hgfac plays a role in rRNA-mediated activation of coagulation. |
format | Online Article Text |
id | pubmed-8759119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-87591192022-01-14 Role of ribosomal RNA released from red cells in blood coagulation in zebrafish and humans Alharbi, Abdulmajeed Iyer, Neha Al Qaryoute, Ayah Raman, Revathi Burks, David J. Azad, Rajeev K. Jagadeeswaran, Pudur Blood Adv Thrombosis and Hemostasis Hemolytic disorders are characterized by hemolysis and are prone to thrombosis. It has previously been shown that the RNA released from damaged blood cells activates clotting. However, the nature of the RNA released from hemolysis is still elusive. We found that after hemolysis, red blood cells from both zebrafish and humans released RNA that contained mostly 5.8S ribosomal RNA (5.8S rRNA), This RNA activated coagulation in zebrafish and human plasmas. By using both natural and synthetic 5.8S rRNA and its truncated fragments, we found that the 3'-end 26-nucleotide-long RNA (3'-26 RNA) and its stem-loop secondary structure were necessary and sufficient for clotting activity. Corn trypsin inhibitor (CTI), a coagulation factor XII (FXII) inhibitor, blocked 3'-26 RNA–mediated coagulation activation in the plasma of both zebrafish and humans. CTI also inhibited zebrafish coagulation in vivo. 5.8S rRNA monoclonal antibody inhibited both 5.8S rRNA– and 3'-26 RNA–mediated zebrafish coagulation activity. Both 5.8S rRNA and 3'-26 RNA activated normal human plasma but did not activate FXII-deficient human plasma. Taken together, these results suggested that the activation of zebrafish plasma is via an FXII-like protein. Because zebrafish have no FXII and because hepatocyte growth factor activator (Hgfac) has sequence similarities to FXII, we knocked down the hgfac in adult zebrafish. We found that plasma from this knockdown fish does not respond to 3'-26 RNA. To summarize, we identified that an rRNA released in hemolysis activates clotting in human and zebrafish plasma. Furthermore, we showed that fish Hgfac plays a role in rRNA-mediated activation of coagulation. American Society of Hematology 2021-11-17 /pmc/articles/PMC8759119/ /pubmed/34547768 http://dx.doi.org/10.1182/bloodadvances.2020003325 Text en © 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. |
spellingShingle | Thrombosis and Hemostasis Alharbi, Abdulmajeed Iyer, Neha Al Qaryoute, Ayah Raman, Revathi Burks, David J. Azad, Rajeev K. Jagadeeswaran, Pudur Role of ribosomal RNA released from red cells in blood coagulation in zebrafish and humans |
title | Role of ribosomal RNA released from red cells in blood coagulation in zebrafish and humans |
title_full | Role of ribosomal RNA released from red cells in blood coagulation in zebrafish and humans |
title_fullStr | Role of ribosomal RNA released from red cells in blood coagulation in zebrafish and humans |
title_full_unstemmed | Role of ribosomal RNA released from red cells in blood coagulation in zebrafish and humans |
title_short | Role of ribosomal RNA released from red cells in blood coagulation in zebrafish and humans |
title_sort | role of ribosomal rna released from red cells in blood coagulation in zebrafish and humans |
topic | Thrombosis and Hemostasis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759119/ https://www.ncbi.nlm.nih.gov/pubmed/34547768 http://dx.doi.org/10.1182/bloodadvances.2020003325 |
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