In humans, non-coding RNA transcripts are involved in many critical events in the life cycle of a cell, from gene expression regulation to protein synthesis by the ribosome. Maintenance of non-coding RNA functions is essential for human physical and neurological development. The long-term goal of our research is to gain an improved understanding of the structures and functions of RNA-protein complexes, in order to develop new approaches to treat human diseases and aging processes.
1) Discovering non-coding RNA-protein interactions affecting gene expression through chromatin state. Epigenetic regulation of chromatin state (transcriptionally active euchromatin versus inactive heterochromatin) controls gene expression patterns in humans. Non-coding RNAs can regulate gene expression by affecting the localization and function of epigenetic modifier proteins, including histone deacetylases. The most well-studied example of a functional non-coding RNA is the X inactive specific transcript (XIST) which controls the function of SHARP and HDAC proteins to silence an entire X chromosome during female embryonic development. An improved understanding of RNA-protein interactions can enable the development of treatments to regulate cancer progression, correct developmental disorders, and slow the aging process. 2) Structural analysis of non-coding RNA and protein complexes from human cells. Some eukaryotic ribonucleoprotein (RNP) complexes including the spliceosome and the ribosome have been examined in great detail, uncovering critical structure-function relationships of non-coding RNAs. Non-coding RNA and protein complexes can control gene expression, hormone receptor responses, and ribosomal function. Through structural studies and mutational analyses, we aim to understand how long non-coding RNAs can localize and organize proteins in the cell in time and space.
3) Uncovering new functions of cancer cell growth associated non-coding RNA transcripts. Therapeutics targeting cancer cell growth and development have mainly focused on protein transcription factors and protein-mediated signaling pathways. Recent bioinformatics studies identified a set of cancer-associated non-coding RNAs whose expression is linked to metastasis and decreased long-term patient survival. We are using a combination of biochemical, biophysical and genomic tools to examine the contributions of cancer-associated ncRNAs to cell growth control.
We are grateful to the following research sponsors for funding and supporting our work: