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Fragments of tRNA suggest a novel

mechanism for cancer progression
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May 7, 2015
Rockefeller University
Researchers discover that particular genetic fragments, of a
type of RNA known as transfer RNA, or tRNA, appear to be
capable of reducing the growth and spread of breast cancer
cells.

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For years, scientists have been puzzled by the

presence of short stretches of genetic material
floating inside a variety of cells, ranging from
bacteria to mammals, including humans. These
fragments are pieces of the genetic instructions
cells use to make proteins, but are too short a
length to serve their usual purpose. Reporting
in Cell, researchers at Rockefeller have
discovered a major clue to the role these
fragments play in the body -- and in the process,
may have opened up a new frontier in the fight
against breast cancer.
Specifically, Sohail Tavazoie and his colleagues discovered that these
particular genetic fragments, of a type of RNA known as transfer RNA (or
tRNA), appear to be capable of reducing the growth and spread of breast
cancer cells. "This is a new basic mechanism the body uses to control the
growth of cancer," says Tavazoie, Leon Hess Associate Professor and
head 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 ways
of curbing cancer that we have never tried before and reveal new basic
insights on how genes are regulated inside our cells."
Scientists have found tRNA fragments in all walks of life, and they
consistently increase in number when cells are exposed to low oxygen
levels and other forms of cellular stress. But their purpose in the body has
remained mysterious. "What those fragments are there for, and their role,
is poorly defined," says Tavazoie.
The research, led by postdoctoral fellow Hani Goodarzi, discovered that
breast cancer cells generate tRNA fragments when exposed to low levels of
oxygen. And cancer cells that carry more of these particular genetic
fragments are less likely to metastasize. What's more, adding these
fragments to cells reduced the growth and progression of cancer; blocking
the fragments, in turn, led to the opposite effect.
Looking closer, the researchers saw that tRNA fragments that come from
specific tRNAs (glutamic acid, aspartic acid, glycine, tyrosine) bind to a key
player in the life cycle of a cancer cell. This key player, known as an
oncogene, normally binds to other RNAs and increases their numbers,
causing them to make more of the oncogenes that help cancer cells divide
and spread. "These tRNA fragments bind the oncogene -- called YBX1 -and push out the other RNAs that encode for oncogenes, reducing cancer
cells' ability to grow and metastasize. By doing so, they represent a new
class of molecules in the cell we call tumor suppressors," says Goodarzi.
These tRNA fragments are demonstrating an entirely novel way of
regulating gene expression, Tavazoie says. By blocking YBX1's ability to
bind other RNAs whose expression YBX1 increases, tRNA fragments are
playing a part in how the body expresses genes.
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It makes sense that the number of tRNA fragments would increase in

periods of cellular stress, such as when the cell is exposed to low oxygen
levels, says Tavazoie. "Cells can sense whether they don't have sufficient
energetic currency that occurs during low oxygen states, and tRNA
fragments help suppress cells' growth rate so they can preserve their
energy and nutrients for when the stress resolves."
Of course, aggressive breast cancer cells often find ways to sidestep the
body's efforts to control them, including those involving these tRNA
fragments. "We're very interested in figuring out how aggressive breast
cancer cells stop the production of tRNA fragments," Tavazoie says. "It's
exciting that these cancer cells are revealing a completely new way by
which expression of oncogenes is regulated as a means of controlling
cancer growth."

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MIND & BRAIN

Story Source:
The above story is based on materials provided by Rockefeller
University. Note: Materials may be edited for content and length.
Rewards
Journal Reference:
1. Hani Goodarzi, Xuhang Liu, Hoang C.B. Nguyen, Steven Zhang, Lisa
Fish, Sohail F. Tavazoie. Endogenous tRNA-Derived Fragments
Suppress Breast Cancer Progression via YBX1 Displacement.
Cell, 2015; 161 (4): 790 DOI: 10.1016/j.cell.2015.02.053

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Rockefeller University. "Fragments of tRNA suggest a novel mechanism for

cancer progression." ScienceDaily. ScienceDaily, 7 May 2015.
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