Search

Your search keyword '"Liang, Jialiang"' showing total 340 results
Start Over Author "Liang, Jialiang"
340 results on '"Liang, Jialiang"'

35. DNA-PKcs has KU-dependent function in rRNA processing and haematopoiesis

Author

Shao, Zhengping, Flynn, Ryan A., Crowe, Jennifer L., Zhu, Yimeng, Liang, Jialiang, Jiang, Wenxia, and Aryan, Fardin

Subjects
Hematopoiesis -- Analysis -- Methods, RNA processing -- Methods -- Analysis, Ribosomal RNA -- Analysis, Protein kinases -- Analysis, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The DNA-dependent protein kinase (DNA-PK), which comprises the KU heterodimer and a catalytic subunit (DNA-PKcs), is a classical non-homologous end-joining (cNHEJ) factor.sup.1. KU binds to DNA ends, initiates cNHEJ, and recruits and activates DNA-PKcs. KU also binds to RNA, but the relevance of this interaction in mammals is unclear. Here we use mouse models to show that DNA-PK has an unexpected role in the biogenesis of ribosomal RNA (rRNA) and in haematopoiesis. The expression of kinase-dead DNA-PKcs abrogates cNHEJ.sup.2. However, most mice that both expressed kinase-dead DNA-PKcs and lacked the tumour suppressor TP53 developed myeloid disease, whereas all other previously characterized mice deficient in both cNHEJ and TP53 expression succumbed to pro-B cell lymphoma.sup.3. DNA-PK autophosphorylates DNA-PKcs, which is its best characterized substrate. Blocking the phosphorylation of DNA-PKcs at the T2609 cluster, but not the S2056 cluster, led to KU-dependent defects in 18S rRNA processing, compromised global protein synthesis in haematopoietic cells and caused bone marrow failure in mice. KU drives the assembly of DNA-PKcs on a wide range of cellular RNAs, including the U3 small nucleolar RNA, which is essential for processing of 18S rRNA.sup.4. U3 activates purified DNA-PK and triggers phosphorylation of DNA-PKcs at T2609. DNA-PK, but not other cNHEJ factors, resides in nucleoli in an rRNA-dependent manner and is co-purified with the small subunit processome. Together our data show that DNA-PK has RNA-dependent, cNHEJ-independent functions during ribosome biogenesis that require the kinase activity of DNA-PKcs and its phosphorylation at the T2609 cluster. The catalytic subunit of DNA-PK autophosphorylates and contributes to ribosome biogenesis and haematopoiesis by binding to the U3 small nucleolar RNA., Author(s): Zhengping Shao [sup.1] [sup.2] , Ryan A. Flynn [sup.3] , Jennifer L. Crowe [sup.1] [sup.4] , Yimeng Zhu [sup.1] [sup.2] , Jialiang Liang [sup.5] , Wenxia Jiang [sup.1] [sup.2] [...]

Published
2020
Full Text
View/download PDF

49. Direct cellular reprogramming techniques for cardiovascular regenerative therapeutics.

Author

He, Xingyu, Dutta, Suchandrima, Liang, Jialiang, Paul, Christian, Huang, Wei, Xu, Meifeng, Chang, Vivian, Ao, Ian, and Wang, Yigang

Abstract

Cardiovascular diseases remain a leading cause of hospitalization affecting approximately 38 million people worldwide. While pharmacological and revascularization techniques can improve the patient's survival and quality of life, they cannot help reversing myocardial infarction injury and heart failure. Direct reprogramming of somatic cells to cardiomyocyte and cardiac progenitor cells offers a new approach to cellular reprogramming and paves the way for translational regenerative medicine. Direct reprogramming can bypass the pluripotent stage with the potential advantage of non-immunogenic cell products, reduced carcinogenic risk, and no requirement for embryonic tissue. The process of directly reprogramming cardiac cells was first achieved through the overexpression of transcription factors such as GATA4, MEF2C, and TBX5. However, over the past decade, significant work has been focused on enhancing direct reprogramming using a mixture of transcription factors, microRNAs, and small molecules to achieve cardiac cell fate. This review discusses the evolution of direct reprogramming, recent progress in achieving efficient cardiac cell fate conversion, and describes the reprogramming mechanisms at a molecular level. We also explore various viral and non-viral delivery methods currently being used to aid in the delivery of reprogramming factors to improve efficiency. However, further studies will be needed to overcome molecular and epigenetic barriers to successfully achieve translational cardiac regenerative therapeutics. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results