KECK SCIENCE DEPARTMENT SEMINAR

 

Transcriptional and post-transcriptional gene regulation mediated by cis-regulatory elements and non-coding RNAs
By
Julia Massimelli
Keck Science
 
From: 11:00 AM To: 12:00 PM
On
Thursday, Feb 20, 2014
At
Burns Lecture Hall, Keck Science Center
In my talk I will be presenting published findings and future steps of a project entitled: Protein-viral long non coding RNA interactions regulating RNA stability Kaposi sarcoma-associated herpesvirus ORF57, also known as Mta (mRNA transcript accumulation), is a multifunctional protein essential for viral gene expression and virus production. We identified a long non-coding polyadenylated nuclear RNA (PAN) as a main target of ORF57 by a genome-wide CLIP (cross-linking and immunoprecipitation) approach. We showed that ORF57 highly increases PAN expression and this depends on a structured RNA element in the 5' PAN, named MRE (Mta responsive element). ORF57 binds to a 9-nt core motif of the MRE to enhance PAN stability. The core motif also binds cellular PABPC1 which interacts with ORF57. Interestingly, PABPC1 was found to relieve the inhibition by PABPC1 to promote PAN expression. Together, our data provide compelling evidence of how RNA-protein interactions can regulate RNA stability. Further studies to characterize the roles of these proteins and their protein partners in PAN accumulation and stability will be discussed. I will also present aims, preliminary results and future steps of a project entitled: Identification of DNA and RNA motifs controlling the expression of the essential gene asd, a key player in amino acid metabolism and bacterial survival Microorganisms utilize aspartic acid as a precursor for the biosynthesis of the essential amino acids lysine, methionine, isoleucine, and threonine. This pathway also produces the precursor for cell-wall cross-linking diaminopimelic acid (DAP), which is required for the synthesis of bacteria cell walls. The asd gene encodes aspartate-ß-semialdehyde dehydrogenase (ASDH), which catalyzes the second reaction of this pathway, consequently, a mutation on the asd gene is lethal without DAP supplementation. ASDH and the entire aspartate pathway are absent in mammals, making this enzyme an attractive target for antibiotic development. Although the asd gene is highly conserved in bacteria, chromosomal neighborhood and asd regulatory sequence elements vary amongst bacterial groups. This work aims to identify regulatory motifs upstream of asd that could serve as targets to shut down asd expression in varying bacteria. We are currently setting up a bioinformatics pipeline for motif discovery upstream of asd. Progress towards currently identified motifs will be discussed along with future directions in the project.
 
 
Seminar Registered by: Velda Yount

 

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