Repetitive Nucleotide Sequences Affect Translation Independently of the Encoded Amino Acids
Nucleotides can affect ribosomal translation. A study by scientists from Johns Hopkins University School of Medicine has discovered that ribosome stalling can come from the RNA sequence and not the encoded aminoacids. A string of adenines was found to be problematic for the translation machinery. The study has been published in Science Advances.
Ribosomes are ribonucleoproteins, found in all living cells, that synthesize proteins from the messenger RNAs. The ribosome binds the mRNA and uses it as a template for linking amino acids in a string that configures a polypeptide chain, the protein. Ribosomes can get stalled in some instances. One of those is upon translation of long adenine stretches, which was attributed to electrostatic interactions between the encoded lysines (AAA) and the ribosome exit tunnel. However, Djuranovic’s team found that ribosomes were more prone to get stalled in lysines coded by the AAA triplet than by the AAG one; and gene constructs with several AAA codons had reduced protein production and mRNA stability. Mutating AAA to AAG had the reverse effect, increasing production and stability. Analyzing vertebrate genomes, the team found out that poly-A stretches of 3 adenines where already counterselected, but some poly(A)s were highly conserved. This implies a possible role as “translational attenuators”, balancing gene dosage.
Djuranovic and colleagues have found a new mechanism through which synonymous mutations can exert biological effects, contributing to the growing evidence that synonymous mutations are not harmless.