University of Pittsburgh Department of Biological Sciences presents:
2019 Fall Seminar Series
Dr. Guramrit Singh
Ohio State University
"How mRNP composition determines mRNA fate?"
Throughout their lifetime, messenger RNAs (mRNA) exist decorated with proteins as mRNA-protein particles, or mRNPs. A key component of all spliced mRNPs is the exon junction complex (EJC), which assembles during pre-mRNA splicing 24 nucleotides (nt) upstream of exon-exon junctions. The stable EJC core thus assembled serves as an interaction platform for peripheral proteins that direct mRNA export, localization, translation and nonsense-mediated mRNA decay (NMD). Both mRNPs and EJCs are widely presumed to be "dynamic" entities that are remodeled during an mRNA’s lifetime. However, this presumption is supported by little direct evidence. We recently discovered that the EJCs, and hence spliced mRNPs, undergo an extensive compositional overhaul after their export to cytoplasm. I will discuss the consequences of this compositional switch for mRNP structure, and for mRNA fate during NMD. I will also discuss our studies on EJC function during zebrafish early embryonic development. We find that EJCs recruited by 3'UTR introns regulate expression of many developmental genes via EJC-dependent NMD. In many instances, 3’UTR introns trigger NMD defying the 50-nucleotide boundary rule, which requires 3'UTR intron to be at least 50 nucleotides downstream of stop codon for it to induce NMD. Overall, mRNP composition dictated by specific gene structures and its spatiotemporal remodeling play an important role in determining mRNA fate.
Monday,November 4, 2019
169 Crawford Hall
11:00 A.M.
10:50 A.M. refreshments
Host: Dr. Andrea Berman