[BK21 Plus Seminar]

▶Subject: tsRNA (a transfer-RNA-derived small non-coding RNA):
Novel insight into mRNA translation and potential target for cancer therapy

▶Speaker: Hak Kyun Kim, Ph. D. (Departments of Pediatrics and Genetics Stanford University School of Medicine)

▶Date: 5:00 PM/Jun, 11(Mon.)/2018

▶Place: Life Science Bidg. #104

▶Abctract
There are tens of thousands of different transfer-RNA-derived small RNAs (tsRNAs) of 18-40 nucleotides in length in mammalian cells. In recent years there is accumulating evidence suggesting that these RNAs can play different yet important roles in gene regulations. Nevertheless, in most cases, the biological roles of these RNAs have yet to be defined. Using a variety of locked nucleic acid/antisense oligonucleotide (LNA/ASO)-mediated strategies, we found that inhibition of one specific tsRNA, induces apoptosis in rapidly dividing cells. Inhibition of the tsRNA but not the mature tRNA reduced the translation of ribosomal protein S28 (RPS28) and S15 (RPS15) mRNAs and led to a block in pre-18S ribosomal RNA processing, and ultimately a decrease in the number of 40S ribosomal subunits. Genetic complementation analyses and multiple approaches establishes that this tsRNA binds to double-stranded target sites in mRNAs and enhances its translation by helping to unfold secondary structure of target sequences.
The systemic delivery of a specific anti-tsRNA oligonucleotides into mice did not cause liver injury in normal mice but induced apoptosis and a significant growth retardation of patient-derived orthotopic hepatocellular carcinomas surgically implanted into mouse livers. Our result establishes a newly defined mRNA translation mechanism and provides a novel target for cancer therapeutics.

▶Inquiry: Prof. Seung-Jae Lee (279-2351)

* This seminar will be given in English.
Please refrain from taking photos during seminars. *