Inactivating mutations in Drosha mediate vascular abnormalities similar to hereditary hemorrhagic telangiectasia (SCIENCE SIGNALING 2018, 11:eaan6831)

報告日期: 2019/04/23
報告時間: 15:10/16:00
報告學生: 饒師維
講評老師: 吳梨華

Inactivating mutations in Drosha mediate vascular abnormalities similar to hereditary hemorrhagic telangiectasia

Jiang X, et al. Jiang et al., Sci. Signal. (2018) 11, eaan6831

SpeakerShih-Wei Jao (饒師維)                  Time2019/04/23, 15:10-16:00

CommentatorProf. Li-Wha Wu (吳梨華老師)    PlaceRoom 602


Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with aberrant vascular development. This disease results from two major mutations in Endoglin (ENG) and activin receptor-like kinase 1 (ACVRL1/ALK1). Typical clinical symptoms of HHT were the telangiectasias and arteriovenous malformations (AVMs). Drosha, a ribonuclease III enzyme, cleaves the primary transcripts of miRNAs to generate precursor miRNAs in the nucleus as well as regulated gene transcription. Previous studies showed that the transforming growth factor-β (TGF-β) family of cytokines plays an important role in the development of vessels as well as their function. Drosha also regulates the TGF-β and BMP pathway through interactions with Smads. Therefore, the goal of this study is to probe the potential connection between Drosha and HHT. First, The Drosha knock-down transgenic Tg (flk1:egfp) zebrafish embryos showed the vascular abnormal development and the increase of vascular permeability. Drosha knock-out mouse revealed dilated and disorganized vasculature, arteriovenous fistulae and hemorrhages like HHT. Second, since the vascular lesions were similar among the Drosha knock-down zebrafish, the knock-out mouse and human HHT patients, the authors started working on analyzing the exome sequence of the 98 individuals who suffered from HHT. In the exome database, it was found that the N-terminal mutations P100L and R279L of Drosha in the pedigree of family 1 and 2 exist. These two mutations were less active enzymes in the pathway of the BMP-Smad–dependent miRNAs. Finally, the exogenous expression of Drosha mutations failed to recover the abnormally vascular development and permeability in the Drosha morphant zebrafish. In conclusion, this study suggested that there’s a potential link between DROSHA missense mutations and hereditary hemorrhagic telangiectasia.


  • A. Hata, Y.G. Chen. TGF-b Signaling from Receptors to Smads. Cold Spring Harb Perspect Biol. (2016)
  • L.M. Botella, V. Albiñana, L. Ojeda-Fernandez, L. Recio-Poveda, C. Bernabéu. Research on potential biomarkers in hereditary hemorrhagic telangiectasia. Frontiers in Genetics. (2015)