Ribosomes Do More than Passively Make Proteins

Researchers from the Stowers Institute for Medical Research have discovered a new function of ribosomes in human cells. The findings, which were published this week in eLife, could lead to further understanding of gene misregulation in human diseases.

“For a long time, many people have viewed ribosomes as a passive player in the cell—a molecular machine that’s just producing proteins,” says senior author Ariel Bazzini. “Now there’s growing evidence that ribosomes regulate gene expression, including in human cells.”

Ribosomes assist with protein biosynthesis by translating the RNA code into a string of amino acids. As part of this process, ribosomes also act as quality control, triggering the destruction of improperly made mRNA. Additionally, growing evidence in various organisms has shown that ribosomes also play a role in affecting the stability of properly processed mRNAs, thereby modulating protein production. The present study shows that ribosomes affect mRNA stability in human cell lines as well.

“We’re seeing that the amount of gene expression is a combination of mRNA production (transcription) and stability,” Bazzini says.

These findings open the door to two exciting research avenues, says Bazzini. The first is better understanding how ribosomes trigger mRNA destruction, the molecular mechanism of which is still unknown. And the second is looking at how this newly discovered regulatory mechanism may be related to genes associated with human diseases. Sequencing of human genomes has shown that individuals sometimes have silent mutations—changes in DNA sequence that do not change the amino acid makeup of the resulting protein—as many amino acids are coded by multiple codons. However, the ‘silent’ mutation might still have an effect if it leads to ribosomes destroying healthy mRNA.

“One of the most basic concepts of biology is how genes are regulated and how those regulations drive cells to become specialized. We’re interested in studying how post-transcription mechanisms work and, in particular, how ribosomes trigger mRNA destruction—how they trigger or recruit factors to carry out this process,” Bazzini says. “Understanding how translation affects mRNA expression at a molecular level allows us to start thinking about how mRNA translation might shape gene expression in cancer, aging, or viral infection.”

Image: A new study using human cell lines provides insight on how instructions embedded within mRNA messages can affect mRNA levels, mRNA stability, and protein production in a translation-dependent manner. Image courtesy of Bazzini Lab.