These findings prompt a further analysis of the effects of initiation codon accessibility on translation initiation in eukaryotes.
The accessibility of mRNA for translation when formulated with PEI was assessed both in vitro and in cultured cells.
The term "epigenetics" refers to heritable changes in gene expression, which are not a result of changes in the DNA sequence, but rather due to alterations related to the packaging (thereby altering DNA accessibility) and/or translation of genetic information [ 6].
Many sRNAs regulate the translation of their target by changing the accessibility of the SD sequence where translation initiation occurs.
The first hypothesis is that there is a set of mRNAs, which is translated inefficiently due to regulation by stress-responsive mechanisms affecting the accessibility of the mRNA for protein translation, such as the need for sRNAs to enable translation [ 41, 15].
mRNA translation efficiency can be affected by the strength of the ribosome binding site (RBS) [ 38], the use of rare codons in the mRNA [ 39, 31], or regulation of the translation-initiation process [ 31], such as accessibility of the mRNA by the translation proteins as might be affected by special features of the 5′ untranslated region (5′UTR) of the mRNA [ 40].
The modulation of AUG codon accessibility may provide a powerful means of translation regulation in eukaryotic cells.
The outcome can be activation or repression of translation by altering ribosome accessibility to the Shine-Dalgarno (SD) sequence and/or start codon (Regnier and Hajnsdorf 2009).
While the presence of general RNA structure in the 5′ UTR can adjust RBS accessibility, many natural and synthetic RNA regulators of translation specifically target the RBS and start codon with either trans-acting RNA-RNA interactions or cis-acting RNA structures that can change conformations and thus switch translation on or off, as described below.
At higher temperatures, this thermosensing region upstream of the coding sequence melts, increasing the accessibility of the RBS leading to an increase in the initiation of translation and, in turn, its protein production rate [1], [4] [6].
RNA structure can play a role in regulating translation through modulating the accessibility of codons.
