Yong Sun Lee, Ph.D., Assistant Professor
During the last decade, one of the most important discoveries in biology has been small non-coding regulatory RNAs, including microRNA (miRNA) and short interfering RNA (siRNA) as two representative classes. While siRNA provided a technical breakthrough for suppression of genes in mammalian cells, miRNA expanded our view of the regulation of gene expression to a post-transcriptional level. Besides miRNA and siRNA, several other types of small RNAs have also been identified. Furthermore, additional novel small RNAs are likely to be discovered, given the short history of the small RNA field and recent innovations in high-throughput sequencing techniques. The biological roles of the most recently discovered small RNAs are poorly understood. Hence, identification and characterization of novel small RNAs await further investigation. The long-term goal of our laboratory is to expand the knowledge of small RNAs. Our current research aims include miRNAs and tRFs (tRNA-derived RNA Fragments)..
Among small RNAs, the most extensively studied are miRNAs that are defined as a short RNA of 17-26 nucleotides (mature miRNA) which is processed from hairpin structured precursors (pre-miRNA) by the enzyme Dicer. miRNAs post-transcriptionally repress gene expression by recognizing complementary target sites in the 3’ untranslated region (UTR) of target mRNAs. miRNAs play roles in vital processes in biology; e.g. cell proliferation, differentiation, metabolism. Aberrant expression of miRNAs can lead to cancer. Currently,our laboratory is investigating miRNAs in lung cancer. We have obtained miRNAomes (global expression profiles of miRNAs) from a lung cancer cell line and a normal lung epithelial cell line. Starting from the two miRNAomes, we aim to identify oncogenic (or tumor suppressive) miRNAs, their downstream target mRNAs, and their upstream regulators that lead to their de-regulation in cancer. Ultimately, we expect to reveal a change in the gene expression network, with miRNAs being a central hub during lung tumorigenesis.
tRFs (tRNA-derived RNA Fragments)
Our laboratory has identified a novel class of short RNAs through the analyses of small RNAomes from prostate cancer cell lines. Briefly, small RNAs of 16-27 nucleotides were isolated, cloned, and sequenced using the 454 high-throughput sequencing technology. Hundreds of these sequences mapped to tRNA loci and constitute the biggest class of small RNAs, barring miRNAs. These tRNA-related sequences, collectively termed tRFs (tRNA-derived RNA Fragments), were classified into three groups, the -5, -3, and -1 series, according to their position relative to mature tRNA. The tRF-5 and -3 series are precisely aligned to the 5’- and 3’-ends of mature tRNA, respectively. The tRF-1 series is located outside of mature tRNA, and its 5’-ends start immediately after the 3’-ends of mature tRNA. Notably, one member of tRF-1 series, tRF-1001, has been shown to be dynamically regulated according to cell proliferation and to be necessary for cell viability. These results, together with reliable detection of tRFs, strongly suggest that tRFs are not random by-products of tRNA degradation, but a novel class of small RNAs with precise sequence structure that deserve further scrutiny. Since tRFs are totally novel molecules, there are numerous questions and research plans. How is tRF-1001 generated? How does tRF-1001 control cell proliferation? Does any tRF other than tRF-1001 exhibit a biological phenotype? There will be many research projects related to answering these questions.