Seminar "RNA decay-linked signaling to maintain cardiac homeostasis."

Dear all,

Cell Signal Unit (Yamamoto Unit) would like to invite you to a seminar by Prof. Keiji Kuba.

We look forward to your participation.

Speaker: Prof. Keiji Kuba

Professor and Chair, Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine

Title: RNA decay-linked signaling to maintain cardiac homeostasis.

Abstract: Cardiovascular diseases are the most common cause of death in developed countries killing more than 15 million people annually in the worldwide. To better understand complex pathophysiology of heart failure, we had conducted large-scale screening for heart failure genes in fruit flies by using cardiac-specific RNAi-silencing in Drosophila. Among the various screening hits, one critical pathway identified was the CCR4-NOT complex, which is a multi-subunit protein complex and regulates global gene expression through mRNA deadenylation and transcription. Heterozygous loss of Cnot3, a subunit of CCR4-NOT complex in mice led to spontaneous impairment of cardiac contractility and increased susceptibility to heart failure (Cell 2010). Transcriptional profiling and in silico network analyses elucidated histone deacetylases (HDACs) and mRNA deadenylases as a central in Cnot3 functions. While down-regulation of transcriptionally active histone marks in Cnot3 haploinsufficient hearts had suggested a crucial role of Cnot3 in regulating epigenetics, our recent comprehensive analyses on cardiac-specific deletion of multiple subunits of the CCR4-NOT in mice revealed more critical role of CCR4-NOT in degrading poly(A) tail of mRNA, so called deadenylation, in cardiac homeostasis. Loss of CCR4-NOT in mouse hearts led to lethal heart failure, which exhibits contractile defects, cardiac hypertrophy and long QT. Bulk mRNA deadenylation was markedly impaired in CCR4-NOT-depleted hearts, which resulted in significant changes in the metabolism of adenosine nucleotides. Importantly, downstream signaling of protein kinase was also influenced by altered nucleotide metabolism. These evidences implicate that there exist non-canonical link of RNA decay and protein kinase signaling to maintain cardiac homeostasis.

Host: 

Tadashi Yamamoto, Cell Signal Unit