Our research aims to understand the role of long intergenic non-coding RNAs (lincRNAs) in establishing the distinct epigenetic states of adult and embryonic cells and their misregulation in diseases such as cancer. To further explore how lincRNAs may define and or drive cell fate decisions we developed computational methods to provide initial hypothesis of their functions. This “guilt by association method” pointed to a clear connection of lincRNAs and numerous cellular pathways ranging from pluripotency, cancer, adipogenesis to parasitology. We have employed systematic computational and experimental approaches that have unraveled a myriad of functional roles for lincRNAs in these pathways. Collectively our studies point to key regulatory roles for lincRNAs across diverse biological pathways, with a common theme of forming ribonucleic-protein complexes that in turn modulate cell fate decisions.
We are actively exploring the roles of lincRNAs in the following areas:
1) ‘onco-RNAs’ and ‘tumor-suppressor-RNAs’ : By analyzing numerous emerging cancer atlases we are identifying candidate RNA genes that are misregulated in cancer and or genetic alteration of RNA genes in caner. Using several cell based assays we are identifying the mechanistic and tumorgenic potential of RNA genes.
2) The role of large RNA genes in cell differentiation: We recently identified numerous lincRNAs that are required or play critical roles during adipogenesis and induced pluripotency amongst others. We are employing large scale Gain and Loss of function experiments to unravel how these RNA based perturbations affect cell circuitry.
3) Structure and Function of Large RNA genes: We are exploring numerous non-canonical Ribonucleic interactions between lincRNAs and proteins that do not contain classic RNA binding domains. Using several approaches we are identifying the diversity of RNA genes bound to epigenetic machinery and how these interactions occur on a structural level.
4) Synthetic RNA Biology: Using RNA as ‘tinker toys’ to build synthetic RNA-Protein interactions to modulate cell fate decisions. We are also exploring using RNA as small molecule screening approaches to identify synthetic RNAs that may guide cellular differentiation.
5) Large RNA genes in Parasites: We recently identified a novel family of telomeric encoded large RNA genes in P. Falciparum Malaria. We are further investigating their potential in regulating virulence genes and or epigenetic regulation of telomeres.
The RNA World
Catalog Number: 57449
John L. Rinn
Half course (spring term). Tu., Th., 1-2:30. EXAM GROUP: 15, 16
This course will introduce classic experiments and examples of functional RNA genes that comprise the ever-emerging RNA world. We will explore diverse classes of RNA genes and their biochemical mechanisms that have defined field, including overviews of relevant technologies leading to these principal findings. Lecture topics will be followed by students reading and presenting related primary literature. Collectively this course will provide an opportunity to explore the wide spectrum of cellular processes involving RNA molecules.
Prerequisite: Life Sciences 1a or equivalent; Life Sciences 1b; SCRB10; MCB 52 or permission of the instructor.