March 21 2017
We had a large number of participants come to the 22nd IRCMS Seminar held on March 22, for which we would like to express our gratitude.
Date: March 22, 2017 (Wed)
Time: 11:00 - 12:00
Venue: 2F Seminar Room, Center for AIDS Research (CAIDS)
Dr. Paul Horton
Prime Senior Researcher
National Institute of Advanced Industrial Science and Technology (AIST), Japan
"Hallmarks of slow translation initiation revealed in mitochondrially localizing mRNA sequences"
The mRNA of some, but not all, nuclear encoded mitochondrial proteins localize to the periphery of mitochondria. Previous studies on yeast and mammalian cells have shown that both the nascent polypeptide chain and an mRNA binding protein play a role in this phenomenon, and have noted a positive correlation between mRNA length and mitochondrial localization. Here, we report the first investigation into the relationship between mRNA translation initiation rate and mRNA mitochondrial localization. Our results indicate that translation initiation promoting factors such as Kozak sequences are associated with cytosolic localization, while inhibiting factors such as 5' UTR secondary structure correlate with mitochondrial localization. Moreover, the frequencies of nucleotides in various positions of the 5' UTR show higher correlation with localization than the 3' UTR. These results suggest that rapid translation initiation may prevent mRNA mitochondrial localization. Interestingly this may explain why short mRNAs, which are thought to initiate translation rapidly, seldom localize to mitochondria. Therefore we propose a model in which translating mRNA has reduced mobility and tends not to reach the mitochondria. Finally, we explore this model with a simulation of mRNA diffusion using previously estimated translation initiation probabilities and confirmed that our model produces localization values similar to those measured in experimental studies.