Scientists from the Johns Hopkins University School of Medicine have discovered that ribosomes can translate mRNA in the Three prime untranslated region (3’UTR). Depletion of the ribosome-recycling protein Rli1 caused piling up of ribosomes at stop codons, but unexpectedly caused them also to start translation of small peptides at the untranslated mRNA region. The finding was published in Cell.
Ribosomes are large molecules, present in all cells, made of RNA and protein. Their function is to translate the information present in messenger RNA (mRNA) sequence into proteins. There are two ribosomal subunits: the small one reads the mRNA, and the large one joins the amino acids to form a polypeptide chain. After protein synthesis, the two ribosomal subunits disassemble. This happens at the termination phase, the last part of the translation process: when a stop codon is reached, the ribosome releases the polypeptide. There is evidence, from in vitro experiments, of the Rli1/ABCE1 protein role in recycling the ribosome subunits after translation. This recycling process dissociates a ribosome from its mRNA molecule so it can start to translate a new mRNA. Rachel Green and her team decide to study the function of Rli1/ABCE1 in vivo. They diminished Rli1 levels in yeast cells, and as they expected, ribosomes accumulated at stop codons. However, they also found ribosomes in the adjacent 3′UTRs, the so-called untranslated region of mRNAs. They also confirmed that ribosomes restarted translation at the 3′UTR without a start codon, as they found small peptides corresponding to the 3′UTR sequence.
Modulating ribosome recycling to adapt to environmental changes
The function of those small peptides is unknown. It could be just a consequence of not recycling ribosomes at a proper rate, but it could be also an adaptation to environmental stress. Translation of the 3′UTRs also happens in wild type cells, emphasizing the importance of ribosome recycling and homeostasis for normal cell function.