Photo of a student working in a lab with Todde Lowe looking over their shoulder.
Lowe and a student in his group. (photo by Carolyn Lagattuta)

Research on tRNA fragments is a relatively new field, as they started gaining recognition and interest only about a decade ago. These fragments are widely varied and perform a myriad of roles in the cell ecosystem, many of which are still being discovered and explored. For example, some tRNA fragments have been recognized to promote cell growth by enabling assembly of ribosomes, the protein factories, whereas other fragments can gum up that same machinery, halting protein production. Other fragments bind key proteins that  can enhance or prevent programmed cell death, and still others get exported in extracellular microvesicles that can communicate information across cells. Together, this mix of many hundreds of types of tRNA fragments add another layer of fine-tuning control to cells, and show promise as a new class of biomarkers for early detection of disease.

The particularities of the chemical bonds in tRNAs had made these molecules difficult to sequence. New sequencing methods have been developed to address these challenges, which has also led to an acceleration of research in this field.
The current lack of a naming system for tRNA fragments makes it very difficult for researchers to compare their discoveries. It also makes it nearly impossible to determine which tRNA the fragment originates from. In humans alone, there are more than 500 different tRNA genes, and understanding which one or more the fragment is derived from is crucial for understanding the role that the fragments play.

“When someone publishes something, you often don’t know what its significance is in the context of everything else that’s been done in the field of tRNA fragments,” Lowe said. “That’s unheard of — it’s frustrating, and it’s not a robust way to do science.”

The new naming scheme makes it easy to locate where in a genome the tRNA fragment comes from and if it is derived from multiple tRNAs or just one. It also identifies if there is variance between the sequenced fragment and the reference tRNA.

Lowe hopes that journal editors will require this new naming system in order to accelerate the process of comparing and integrating findings across the wide range of research that involves tRNA fragments.

Lowe believes some researchers may be hesitant to stop using the original names they’ve assigned to tRNA fragments discovered in their labs, but suggests researchers can use their chosen identifiers in papers as long as they give reference to the systematic name as well. The many collaborating co-authors on the paper who helped shape the standard will be important in getting the word out about this new system and encouraging other scientists to adopt it.

“We were thrilled to work with a group of scientists who had a vested interest in putting away individual preferences for the good of the field and produced a naming scheme that will make it easier to advance this growing field,” Kay said.

In the future, Lowe and his group intend to merge the naming software with another of their programs, which maps misincorporation-inferred modifications in tRNA sequencing reads. They will also apply the new naming system to publicly available data sets, and incorporate these into the Genomic tRNA Database (GtRNAdb), which is maintained by Lowe’s group.

Lowe is excited to see what discoveries will be enabled by the adaption of this naming system.

“There’s a ton more of these tRNA fragments,” Lowe said. “We’ve just seen the tip of the iceberg, which is why this is so important.”