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A New Direction in Ribosomes

October 23, 2015

BioE Assistant Professor Nikolai Slavov has shown that cells build different ribosomes that likely not only assemble amino acids into proteins but also regulate protein production.

Source: News @ Northeastern

Nikolai Slavov, a new assis­tant pro­fessor in the Depart­ment of Bio­engi­neering, wasn’t looking to upend con­ven­tional wisdom when he set out to mea­sure pro­tein levels in ribo­somes, the par­ti­cles in cells that syn­the­size all the other pro­teins that keep living things—from ani­mals to bacteria—functioning. He just wanted to under­stand what was dri­ving some of the yeast cells in his lab to grow faster than others.

Now, in a new paper pub­lished Thursday in the journal Cell Reports, Slavov and his col­leagues have cast ribo­somes in a new light—research that could have impli­ca­tions for new direc­tions in fields from tissue engi­neering to cancer therapeutics.

Slavov’s find­ings indi­cate that ribo­somes not only assemble pro­teins by linking together the spe­cific chem­ical groups, or “amino acids,” that make up each pro­tein; they also appear to reg­u­late that pro­duc­tion. In a sense, a bio­log­ical con­struc­tion worker has now become a gen­eral con­tractor. Ribo­somes may deter­mine, for example, how many of which types of pro­tein roll off the assembly line.

What I have found sug­gests that ribo­somes are likely to be among the pri­mary fac­tors in not just syn­the­sizing pro­teins but deter­mining which pro­tein mol­e­cules are made in which tissue type,” says Slavov. “In tissue engi­neering, if we want to repro­gram, say, an embry­onic stem cell to make a heart cell, we know now that we may have to take into account how to influ­ence the ribosome.”

The building blocks of life

Pro­teins are, essen­tially, the building blocks of life. They are large, com­plex mol­e­cules made up of varying chains of amino acids, and they serve a mul­ti­tude of func­tions: as struc­tural mate­rials (bones, mus­cles, hair), enzymes (pro­teins that spark bio­log­ical reac­tions), and mes­sen­gers (some hormones).

Cer­tain core pro­teins reside inside each ribosome—they are what enable the ribo­some to do its protein-​​assembly job. For decades sci­en­tists believed that all ribo­somes had the same com­po­si­tion, that is, they all con­tained 80 core pro­teins: You’d seen the com­po­si­tion of one ribo­some, you’d seen them all.

But in his new study, Slavov revealed that may not be the case. Using the most up-​​to-​​date tech­niques of mass spec­trom­etry, he painstak­ingly mea­sured the ribo­some pro­teins in sam­ples of yeast cells and mouse embry­onic stem cells—the dis­parate cell types would permit him to gen­er­alize his results.

Ribo­somes, his data indi­cated, are not all cut from the same cloth: their com­po­si­tion, and hence their func­tion, varies.

If it is causal…it will open the pathway to new cancer ther­a­pies that are directed toward ribo­somes specif­i­cally
—Slavov said

From pas­sive to active role

Ribo­somes get their protein-​​assembly instructions—which amino acids to link in a chain and in what order they should link—from a mol­e­cule called mes­senger RNA, or mRNA. Think of mRNA as DNA’s Uber ser­vice: mRNA picks up instruc­tions from genes and car­ries them to the ribo­somes, which then assemble the proteins.

Until now, says Slavov, sci­en­tists believed that ribo­somes in unper­turbed cells had a pas­sive role in the expres­sion of genetic infor­ma­tion. That is, in the ribo­some, the core pro­teins simply fol­lowed the mRNA instruc­tions; they did not deter­mine how often those instruc­tions were trans­lated and, in turn, how many mol­e­cules of that par­tic­ular pro­tein were produced.

Every­thing changes, how­ever, if the com­po­si­tion of the core pro­teins varies. For example, cer­tain can­cers, such as uterine cancer, are asso­ci­ated with muta­tions in genes that code for a par­tic­ular core pro­tein, per­haps affecting that protein’s proper func­tion. The altered com­po­si­tion of the pro­teins, says Slavov, might boost the ribosome’s capacity for pro­tein syn­thesis and there­fore pro­mote cancer cell growth.

This is not proven yet,” he cau­tions. The next step is to test the hypoth­esis fur­ther to show that there’s an actual cause-​​and-​​effect rela­tion­ship between the core pro­tein func­tion and cancer cell growth. “If it is causal,” he says, “it will open the pathway to new cancer ther­a­pies that are directed toward ribo­somes specifically.”

The other con­trib­u­tors to the research are from Har­vard Uni­ver­sity, Leiden Uni­ver­sity, and the Uni­ver­sity Med­ical Center Utrecht.