PUBLICATION
Role of Ribosomal RNA Released from Red Cells in Blood Coagulation in Zebrafish and Humans
- Authors
- Alharbi, A., Iyer, N., AlQaryoute, A., Raman, R., Burks, D., Azad, R., Jagadeeswaran, P.
- ID
- ZDB-PUB-210922-37
- Date
- 2021
- Source
- Blood advances 5(22): 4634-4647 (Journal)
- Registered Authors
- Jagadeeswaran, Pudur
- Keywords
- none
- MeSH Terms
-
- Animals
- Blood Coagulation
- Erythrocytes
- Factor XII
- Humans
- RNA, Ribosomal*/genetics
- Zebrafish*
- PubMed
- 34547768 Full text @ Blood Adv
Citation
Alharbi, A., Iyer, N., AlQaryoute, A., Raman, R., Burks, D., Azad, R., Jagadeeswaran, P. (2021) Role of Ribosomal RNA Released from Red Cells in Blood Coagulation in Zebrafish and Humans. Blood advances. 5(22):4634-4647.
Abstract
Hemolytic disorders are characterized by hemolysis and are prone to thrombosis. Previously, it has been shown that the RNA released from damaged blood cells activates clotting. However, the nature of RNA released from hemolysis is still elusive. We found that after hemolysis, RBCs from both zebrafish and humans released 5.8S rRNA. This RNA activated coagulation in zebrafish and human plasmas. 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 of both zebrafish and human plasma. 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 activates normal human plasma but did not activate FXII-deficient human plasma. Taken together, these results suggested that the activation of zebrafish plasma is via FXII-like protein. Since zebrafish has no FXII and 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. In conclusion, we identified 5.8S rRNA released in hemolysis activates clotting in human and zebrafish plasma. Only 3'-end 26 nucleotides of the 5.8S rRNA is needed for the clotting activity. Furthermore, we showed that fish Hgfac plays a role in 5.8S rRNA-mediated activation of coagulation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping