Investigating the Role of Long-noncoding RNA Structures and Interactions in Human Cancer Cells

Description

Accumulating evidences have shown that lncRNAs play an important role in the development of cancer. The knowledge of lncRNA secondary structures and especially their functional structural elements and also the information of lncRNA interacting proteome are the two basis for further studies of the role of lncRNAs. On this basis, the interplay between lncRNA secondary structures and their interacting proteomes is the key to understanding the molecular mechanism of lncRNA functions and regulations in cancer.In this collaborative project, we will develop new high-throughput techniques to probe transcriptome-wide lncRNA secondary structures and also G-quadruplexes in different cancer cell lines. We will design a new bioinformatics algorithm to reconstruct cell-specific lncRNA secondary structural models based on experimental data, and to identify a set of lncRNAs with secondary structural elements important in cancers through comparative analysis. We will then focus on some lncRNAs in this set, e.g., MALAT1, to experimentally characterize their interacting proteomes by using ChIRP-MS. We will analyze and validate the interplay of the secondary structures and the interacting proteomes of MALAT1 and other important lncRNAs in different cancer cell lines.This collaborative project combines interdisciplinary experimental and computational approaches and integrates the two research groups' years of research experience in RNA structure and RNA-protein interactions. It uses and improves the cutting-edge techniques to study molecular mechanisms of lncRNA’s role in cancer. It will advance our understanding of lncRNAs in both basic and translational research.