PUBLICATION
Deregulation of Drosha in the pathogenesis of hereditary hemorrhagic telangiectasia
- Authors
- Hata, A., Lagna, G.
- ID
- ZDB-PUB-190312-10
- Date
- 2019
- Source
- Current opinion in hematology 26(3): 161-169 (Review)
- Registered Authors
- Hata, Akiko
- Keywords
- none
- MeSH Terms
-
- Animals
- Humans
- Mice
- MicroRNAs*/genetics
- MicroRNAs*/metabolism
- Mutation, Missense*
- Ribonuclease III*/genetics
- Ribonuclease III*/metabolism
- Signal Transduction*
- Telangiectasia, Hereditary Hemorrhagic*/enzymology
- Telangiectasia, Hereditary Hemorrhagic*/genetics
- Telangiectasia, Hereditary Hemorrhagic*/pathology
- Zebrafish
- PubMed
- 30855334 Full text @ Curr. Opin. Hematol.
Citation
Hata, A., Lagna, G. (2019) Deregulation of Drosha in the pathogenesis of hereditary hemorrhagic telangiectasia. Current opinion in hematology. 26(3):161-169.
Abstract
Purpose of review The TGFβ (transforming growth factor β) superfamily - a large group of structurally related and evolutionarily conserved proteins - profoundly shapes and organizes the vasculature during normal development and adult homeostasis. Mutations inactivating several of its ligands, receptors, or signal transducers set off hereditary hemorrhagic telangiectasia (HHT), a disorder that causes capillary networks to form incorrectly. Drosha, an essential microRNA-processing enzyme, also interfaces with TGFβ signal transducers, but its involvement in vascular conditions had not been tested until recently. This review summarizes current evidence that links mutations of Drosha to HHT.
Recent findings Genetic studies have revealed that rare missense mutations in the Drosha gene occur more commonly among HHT patients than in healthy people. Molecular analyses also indicated that Drosha enzymes with HHT-associated mutations generate microRNAs less efficiently than their wild-type counterpart when stimulated by TGFβ ligands. In zebrafish or mouse, mutant Drosha proteins cause the formation of dilated, leaky blood vessels deprived of capillaries, similar to those typically found in patients with HHT.
Summary Recent evidence suggests that Drosha-mediated microRNA biogenesis contributes significantly to the control of vascular development and homeostasis by TGFβ. Loss or reduction of Drosha function may predispose carriers to HHT and possibly other vascular diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping