Seminar by Prof. Toshifumi Inada "Novel mRNA and protein quality control systems induced by aberrant translation"
Cell Signal Unit(Yamamoto Unit) would like to invite you to a seminar by Prof. Toshifumi Inada.
Date: Monday, April 8th
Time: 16:00 - 17:00
Venue: C015, Lab1
Speaker: Prof. Toshifumi InadaGaduate School of Pharmaceutical Sciences & Faculty of Pharmaceutical Sciences, Tohoku University
Graduate School of Pharmaceutical Sciences, Tohoku University
Title: Novel mRNA and protein quality control systems induced by aberrant translation
Abstract: Cells have mRNA surveillance systems to recognize aberrant translation elongation and termination, and eliminate aberrant mRNAs in cells. NMD (Nonsense-Mediated mRNA Decay) is the most characterized mRNA surveillance system that recognizes and eliminates aberrant mRNAs containing a premature termination codon. NSD (NonStop Decay) system rapidly degrades nonstop mRNA that lacks a termination codon and is produced mainly by polyadenylation within an ORF. NGD (No-Go Decay) quality control system recognizes the stalling of ribosomes during translational elongation and induces endonucleolytic cleavage of the mRNA in the vicinity of the stalled site that leads to rapid mRNA degradation.
We have recently demonstrated that rapid proteasomal degradation of aberrant proteins derived from aberrant mRNAs plays an important role in preventing the expression of abnormal proteins as well as in promoting rapid mRNA decay by mRNA surveillance systems. An essential NMD factor Upf1p stimulates the degradation of a carboxyl-terminal truncated product derived from specific PTC-containing mRNAs. In NSD and NGD, translation arrest induced by a nascent peptide with positively charged residues results in co-translational degradation of the arrested protein product by the proteasome. Two distinct E3 ubiquitin ligases, Ltn1 and Not4, are involved in the degradation of arrest products associated with stalled ribosome. Not4, a component of Ccr4-Not deadenylase complex, is associated with ribosome and involved in protein degradation induced by aberrant translation elongation. We also found that novel complex Dom34:Hbs1 stimulates the degradation of stop-codon-less and nonstop mRNAs by dissociating a ribosome that is stalled at the 3’ end of the mRNA, which makes the released mRNA more vulnerable to nucleolytic attack, and that Dom34:Hbs1 plays important roles in both NSD and NGD.
Tadashi Yamamoto, Cell Signal Unit
We look forward to seeing many of you.
Cell Signal Unit (Yamamoto Unit)