Biology subjects

Horton, P.

Publications and source records attributed to Horton, P..

2 recordsLinked to original sources

bioRxiv2019

A Simulation Study of mRNA Diffusion and Mitochondrial Localization

BackgroundWe have observed a negative correlation between rapid translation initiation of mRNA and their localization at mitochondria. One potential explanation of this anti-correlation is that mRNA which initiate translation away from mitochondria experience a significant drop in mobility and thus remain there. To explore this possibility, we conducted an initial simulation of diffusion and compared those results to gene-specific experimental measurements of mRNA mitochondrial localization.\n\nMethodsHere, we conduct a follow-up simulation study to complement the initial one. In particular we attempt a more quantitative analysis, deriving linear scale estimates of mitochondrial localization probability from sequencing based measurements. We compare this data to simulated mitochondrial localization probabilities under a variety of simulation parameter settings.\n\nConclusionsWe conclude that if a change in mRNA mobility after translation initiation is a significant factor in explaining the negative correlation between mRNA localization and translation initiation efficiency, then 1) the effective diffusion coefficient of mRNA must be strongly reduced upon translation initiation (e.g. 20x) and 2) mRNA molecules which have not yet initiated translation when approaching a mitochondrial surface must have a non-zero probability of anchoring there.

bioinformatics↗

bioRxiv2019

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 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 indicate that mitochondrial localization is associated with slow translation initiation. Interestingly this may help explain why short mRNAs, which are thought to initiate translation rapidly, seldom localize to mitochondria. We propose a model in which translating mRNA has reduced mobility and tends not to reach mitochondria. Finally, we explore this model with a simulation of mRNA diffusion using previously estimated translation initiation probabilities, confirming that our model can produce localization values similar to those measured in experimental studies.

molecular biology↗