[대학원 생명과학과 세미나 안내]

 

연사 : 윤제현 교수(Medical University of South Carolina))


연제 : RNA methylation and novel microRNA-binding proteins in human aging

 

일시 : 2016년 5월 11일 (수) 오후 4시

 

장소 : 하나과학관 A동 207호


초청교수 : 김윤기 교수


Abstract


  While the role of signaling pathway, energy metabolism, and transcription regulation in human aging has been studied extensively, recent studies have shown that post-transcriptional regulation also plays an essential role. In Peripheral Blood Mononuclear Cells (PBMCs) and human diploid fibroblasts (HDFs), models of human aging and cellular senescence, RNA profiling analyses have revealed that noncoding RNA levels fluctuate greater than mRNAs implicating their importance in mRNA decay, translation, and modification. Here, we report that a subset of miRNAs are differentially expressed in PBMCs from old cohorts compared to young and that this occurs concomitantly with differential levels of N6-methyladenosine (m6A) modification of specific mRNAs. Among various mRNAs with m6A modification, AGO2 mRNA methylation decreased in old PBMCs cohorts with an accompanying depletion of its mRNA and protein. Based upon this, we interpret that differential expression of AGO2, a key regulator of miRNAs, mediates differential expression of miRNA mediators in cellular senescence and aging. Reduction of miRNAs predicts accumulation of age-specific and senescence-associated proteins escaping from miRNA-mediated translation repression. Taken together, our data elucidate molecular mechanism of mRNA methylation to maintain AGO2 and miRNAs levels in human aging and cellular senescence.
  AGO2 depletion in human aging and cellular senescence predicts presence of novel miRNA-binding proteins (miRBPs) to maintain miRNA-mediated gene silencing pathway. We recently performed protein microarray analysis to identify novel miRBPs by utilizing miRNA let-7b and identified 60 proteins interacting with let-7b. Single-molecule biophysical analysis revealed that these miRBPs promote or inhibit AGO2 function by direct interaction with let-7b. Thus, our results demonstrate the role of novel miRBPs to keep miRNA-mediated gene silencing pathway active during the processes of human aging and cellular senescence.