Leaders in Pharmaceutical Business Intelligence (LPBI) Group

2:45 – 3:15, 2014, Jeannie Lee “Regulatory interactions between RNA and Polycomb repressive complex 2”

Reporter: Aviva Lev-Ari, PhD, RN

LIVE from Kresge Auditorium @MIT

Key concepts captured:

• Xist – XCI – is essential through female life
• Myelomonoclonal, hisiocytic Sarcoma
• a primary HSC defect – aberrant differentiation/maturation
• deletion exists –>> genome wide causing leukehmia in balood cells.
• Xist – noncoding RNA – responsible for health
• XCI model: Recruiting and Loading,  biologically separate from upregulation
• Polycomb Repressive Complex 2
• PRC2 large RNA interactome –>> bind RNA
• RNA EMSA with core PRC2 – a range of binding affinities
• Disassociation constants (Kd): PRC2 has huge preference for RepA over nonspecific RNAs
• EZH2 has very high affinity for RNA, premiscous
• EED does not bind RNA at all
• EED weakekns the strength of EZH2:RNA interactions
• Presence of RNA inhibits PRC2 HMTase -inhibition is positively correlated with Kd.
• JARID2 – regulates PRC2, it attenuates RNA binding of PRC2, in presence of PRC2 affinity drops
• RNA recruite also blocks HMTase
• SMN Lead optimization in vivo works well and therapeutic applications are been explored

2:45 – 3:15, 2014,  Jeannie Lee  “Regulatory interactions between RNA and Polycomb repressive complex 2”

@MIT – Summer Symposium 2014: RNA Biology, Cancer and Therapeutic Implications, June 13, 2014 8:30AM – 4:30PM, Kresge Auditorium @MIT

http://ki.mit.edu/news/symposium

REALTIME event coverage for the Scientific Media by Dr.  A. Lev-Ari 

in Open Access Scientific Journal of Leaders in Pharmaceutical Business Intelligence (LPBI)

http://pharmaceuticalintelligence.com

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Jeannie Lee, MD, PhD 
Professor of Genetics (and Pathology), Massachusetts General Hospital 
Investigator, Howard Hughes Medical Institute

Jeannie T. Lee is an Investigator of the Howard Hughes Medical Institute and Professor of Genetics (and Pathology) at Harvard Medical School and the Massachusetts General Hospital (MGH). She is also the Scientific Founder of RaNA Therapeutics, a company that harnesses the potential of long noncoding RNAs to treat disease. Dr. Lee specializes in the study of epigenetic regulation by long noncoding RNAs (lncRNA). Using X-chromosome inactivation (XCI) as a model, her laboratory has made several contributions to our understanding of RNA-directed chromatin change, including the role of RNA in targeting Polycomb complexes and the mechanisms of repression by antisense RNA. She received her BA in biochemistry and molecular biology from Harvard University, where she worked on antisense repression of transposition with Nancy Kleckner. She obtained MD-PhD degrees from the University of Pennsylvania School of Medicine, where she studied epigenetic regulation of X-linked diseases with Robert L. Nussbaum. At the Whitehead Institute/MIT, her postdoctoral work with Rudolf Jaenisch delineated the X-inactivation center. She has served as Chief Resident of Clinical Pathology at MGH, and received both the Basil O’Connor Scholar Award (March of Dimes) and the Pew Scholars Award (Pew Foundation) as a young investigator. Dr. Lee has been awarded a Distinguished Graduate Award of the University of Pennsylvania School of Medicine, and currently holds a MERIT Award from the NIH. She is also the recipient of the 2010 Molecular Biology Prize from the National Academy of Sciences, U.S.A, is a Fellow of the American Association for the Advancement of Science (AAAS), and has served on the Board of Directors for the Genetics Society of America.