JUN 06, 2016 2:51 PM PDT

Changes In tRNA Levels Shown to Drive Cancer Metastasis

WRITTEN BY: Carmen Leitch
It’s long been accepted that the human genome instructs our bodies on what proteins to make using molecules called tRNAs. They have seemed to simply be an innocuous participant in a much bigger process without much impact on what happens in a cell. The interaction of tRNA and mRNA is described in the video below.

In new work published in the journal Cell, researchers are challenging the paradigm that tRNA has no other roles or influence on the cell. It appears as though fluctuations in the abundance of tRNAs have a big impact on everything from single cells to disease processes. “We’ve long thought of these molecules as little more than middle men participating in the process of translating proteins,” said Sohail Tavazoie, a physician and Associate Professor at Rockefeller University’s Elizabeth and Vincent Meyer Laboratory of Systems Cancer Biology.

The work has been aided by improved technology, as tRNAs have traditionally been very challenging to analyze. Authors of the paper utilized approaches from next-generation sequencing to devise a new method that allows them to look at tRNA levels in depth.  

Once they found a way to measure the levels of tRNAs, the research team sampled different kinds of tumors, primary and metastatic, from breast cancer patients and compared them to breast tissue samples from healthy people.
                    Samples from non-metastatic (left) and metastatic breast cancer (right) cells showing enhanced expression of a specific gene in metastatic tumors because those cells have increased levels of a tRNA called GluUUC.
Intriguingly, it was found that the amount of two very specific tRNAs was significantly higher in metastatic tumors and cells than it was in both primary tumors that did not metastasize or healthy samples. “There are six different ways to encode for the protein building block arginine,” said Tavazoie. “Yet only one of those - the tRNA that recognizes the codon CGG - was associated with increased metastasis.” The other tRNA that was elevated in metastatic samples was one that recognizes the codon GAA and encodes for glutamic acid.
                              
It was hypothesized that elevated levels of these tRNAs may be what drives metastasis. Using mouse models of non-metastatic primary tumors, the scientists increased the levels of two the tRNAs, and found that these cells became much more invasive and metastatic. To further validate the idea, the inverse experiment was also performed. This time, when the amount of these tRNAs was reduced in metastatic cells, a decrease in the incidence of metastases in the animals was observed, confirming their hypothesis.

So how is the tRNA causing metastasis? The team decided to look at protein levels and see how they varied when levels of the two tRNAs changed.  “We found global increases in many dozens of genes, so we analyzed their sequences and found that the majority of them had significantly increased numbers of these two specific codons,” explained Tavazoie.

From their list of genes that had increased in abundance, they then altered two of them with a ’silent’ mutation. These types of mutations take advantage of the redundancy in the genetic code, and even with a single base pair change will encode for the same amino acid. When they did that, it was observed that elevating tRNA levels no longer resulted in metastasis. Tavazoie commented that “it is remarkable that within a single cell type, synonymous changes in genetic sequence can dramatically affect the levels of specific proteins, their transcripts, and the way a cell behaves.”

Sources: Cell, The Rockefeller University
About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
DEC 24, 2020
Genetics & Genomics
After Chromosomes Shatter, Cancer Cells Can Become Drug-Resistant
DEC 24, 2020
After Chromosomes Shatter, Cancer Cells Can Become Drug-Resistant
Many types of cells have to be replenished throughout our lives, and cells divide to replace those that are damaged or w ...
DEC 25, 2020
Cell & Molecular Biology
Immune Protein Has a Surprising Role in Cell Adhesion
DEC 25, 2020
Immune Protein Has a Surprising Role in Cell Adhesion
During development, cells multiply to grow the animal, and those cells have to organize properly and differentiate into ...
JAN 28, 2021
Cell & Molecular Biology
Gene Variants Affecting an Ion Channel Alter Parkinson's Disease Risk
JAN 28, 2021
Gene Variants Affecting an Ion Channel Alter Parkinson's Disease Risk
These variants can raise, or lower the risk of the disease, and now researchers have learned how they work.
FEB 09, 2021
Immunology
Putting the Kibosh on HIV's Stealth Tactics
FEB 09, 2021
Putting the Kibosh on HIV's Stealth Tactics
The human immunodeficiency virus or HIV is always one step of the immune system, a tactic that makes it impossible to co ...
FEB 13, 2021
Cell & Molecular Biology
The Secret to the Success of World's Fastest Growing Plant
FEB 13, 2021
The Secret to the Success of World's Fastest Growing Plant
The fastest growing plant in the world is known as duckweed or Wolffia. It grows on every continent except Antarctica, h ...
FEB 21, 2021
Genetics & Genomics
How Spina Bifida Can Arise From Spontaneous Mutations
FEB 21, 2021
How Spina Bifida Can Arise From Spontaneous Mutations
Spina bifida is a birth defect that happens when the spinal cord of a developing infant doesn't form correctly, because ...
Loading Comments...