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Web End = Mol Biol Rep (2016) 43:295304 DOI 10.1007/s11033-016-3954-6
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Web End = RNA fragments mimicking tRNA analogs interact with cytochrome c
Roza Pawlowska1 Magdalena Janicka1 Dominika Jedrzejczyk1
Arkadiusz Chworos1
Received: 29 June 2015 / Accepted: 11 February 2016 / Published online: 18 February 2016 Springer Science+Business Media Dordrecht 2016
Abstract In times, when drug seeking assays focus on the natural molecular triggers and their analogs, a deeper insight into molecular mechanisms governing the initial step of intrinsic apoptosis (cytochrome c release) is essential to suppress the immortality of pathologically changed cells. In this study, we examined RNA molecules mimicking mitochondrial tRNAs interacting with cytochrome c and possibly affecting its cellular function. tRNA analogs were designed and synthesized prior to the conformational analysis and gel assays clearly stating the nucleic acid protein complex formation. The circular dichroism spectroscopic (CD) and microscale thermophoresis examination revealed the structural and conformational differences between four tRNA analogs in their interactions with cytochrome c. Obtained CD spectra and gel studies resulted in the complex ratio estimation and conclusion that not only the complex formation may be preferential towards specic tRNAs present in the cell, but nucleobase modications are not essential for such interaction.
Keywords tRNA analogs Cytochrome c Circular
dichroism tRNA structure Apoptosis Microscale
thermophoresis
Introduction
The tRNA molecules play an essential role as a key element in the protein biosynthesis. Over 450 tRNA genes have been already reported in the human genome, from which 22 are present in human mitochondrial genome [1, 2]. The pool of tRNAs is enriched by chemical nucleoside modications, which are crucial for structure, function and stability of tRNAs molecules [3]. The presence of modied nucleobases in tRNA is correlated with occurrence of cancers, neurological disorders, diabetes type II and mitochondrial related diseases [3]. It was also shown, that variable mutation in mitochondrial tRNA genes [4] and mitochondrial tRNA cleavage [5] leads to cellular disorder. Recent studies indicate, that tRNA molecules may affect the regulation of gene expression in response to the stress conditions [6] and are involved in...