Fragments of TRNA Suggest a Novel Mechanism for Cancer Progression

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Fragments of tRNA suggest a novelmechanism for cancer progression

May 7, 2015

Rockefeller University

Researchers discover that particular genetic fragments, of atype of RNA known as transfer RNA, or tRNA, appear to becapable of reducing the growth and spread of breast cancercells.

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For years, scientists have been puzzled by thepresence of short stretches of genetic materialfloating inside a variety of cells, ranging frombacteria to mammals, including humans. Thesefragments are pieces of the genetic instructionscells use to make proteins, but are too short alength to serve their usual purpose. Reportingin Cell, researchers at Rockefeller havediscovered a major clue to the role thesefragments play in the body -- and in the process,may have opened up a new frontier in the fightagainst breast cancer.

Specifically, Sohail Tavazoie and his colleagues discovered that theseparticular genetic fragments, of a type of RNA known as transfer RNA (ortRNA), appear to be capable of reducing the growth and spread of breastcancer cells. "This is a new basic mechanism the body uses to control thegrowth of cancer," says Tavazoie, Leon Hess Associate Professor andhead of the Elizabeth and Vincent Meyer Laboratory of Systems Cancer

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Biology. "We plan to explore it further, so hopefully it will open up new waysof curbing cancer that we have never tried before and reveal new basicinsights on how genes are regulated inside our cells."

Scientists have found tRNA fragments in all walks of life, and theyconsistently increase in number when cells are exposed to low oxygenlevels and other forms of cellular stress. But their purpose in the body hasremained mysterious. "What those fragments are there for, and their role,is poorly defined," says Tavazoie.

The research, led by postdoctoral fellow Hani Goodarzi, discovered thatbreast cancer cells generate tRNA fragments when exposed to low levels ofoxygen. And cancer cells that carry more of these particular geneticfragments are less likely to metastasize. What's more, adding thesefragments to cells reduced the growth and progression of cancer; blockingthe fragments, in turn, led to the opposite effect.

Looking closer, the researchers saw that tRNA fragments that come fromspecific tRNAs (glutamic acid, aspartic acid, glycine, tyrosine) bind to a keyplayer in the life cycle of a cancer cell. This key player, known as anoncogene, normally binds to other RNAs and increases their numbers,causing them to make more of the oncogenes that help cancer cells divideand spread. "These tRNA fragments bind the oncogene -- called YBX1 --and push out the other RNAs that encode for oncogenes, reducing cancercells' ability to grow and metastasize. By doing so, they represent a newclass of molecules in the cell we call tumor suppressors," says Goodarzi.

These tRNA fragments are demonstrating an entirely novel way ofregulating gene expression, Tavazoie says. By blocking YBX1's ability tobind other RNAs whose expression YBX1 increases, tRNA fragments areplaying a part in how the body expresses genes.

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It makes sense that the number of tRNA fragments would increase inperiods of cellular stress, such as when the cell is exposed to low oxygenlevels, says Tavazoie. "Cells can sense whether they don't have sufficientenergetic currency that occurs during low oxygen states, and tRNAfragments help suppress cells' growth rate so they can preserve theirenergy and nutrients for when the stress resolves."

Of course, aggressive breast cancer cells often find ways to sidestep thebody's efforts to control them, including those involving these tRNAfragments. "We're very interested in figuring out how aggressive breastcancer cells stop the production of tRNA fragments," Tavazoie says. "It'sexciting that these cancer cells are revealing a completely new way bywhich expression of oncogenes is regulated as a means of controllingcancer growth."

Story Source:

The above story is based on materials provided by RockefellerUniversity. Note: Materials may be edited for content and length.

Journal Reference :

1. Hani Goodarzi, Xuhang Liu, Hoang C.B. Nguyen, Steven Zhang, LisaFish, Sohail F. Tavazoie. Endogenous tRNA-Derived FragmentsSuppress Breast Cancer Progression via YBX1 Displacement.Cell, 2015; 161 (4): 790 DOI: 10.1016/j.cell.2015.02.053

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Fragments of TRNA Suggest a Novel Mechanism for Cancer Progression