Story

By applying a high-resolution ribosome profiling method developed at RIKEN Pioneering Research Institute (PRI), Dr. Taisei Wakigawa uncovered hidden translation events that reveal new layers of mitochondrial gene expression.

Goosebumps in the Data

Mitochondria have long challenged researchers with a fundamental question: how does protein synthesis end? Although the mechanisms of mitochondrial translation termination have been studied for over a decade, the process remained difficult to monitor directly.

Building on the earlier study in Molecular Cell, Dr. Taisei Wakigawa applied a high-resolution mitochondrial ribosome profiling method to visualize translation termination at single-codon resolution.

“At first, everything looked exactly as expected,” he recalls.

Cells lacking mitochondrial translation release factors showed ribosomes stalled at stop codons, confirming that the method was working. Then an unexpected signal appeared. Cells lacking mitochondrial release factors showed ribosomes stalled at stop codons, confirming that the approach was working. Then the data took an unexpected turn.

“I looked at the data and thought, ‘What is this?’ When I examined the stalling sequence, I realized that an out-of-frame stop codon was hidden within it . I still remember getting goosebumps. Once we started looking from that perspective, we found the same phenomenon in many different places.”

Instead of dismissing the observation, Dr. Wakigawa immediately discussed it with Chief Scientist Shintaro Iwasaki.

“I took the data to him, and he immediately said, ‘This is exciting! Let’s keep going.’ That’s what I value about our lab—we turn unexpected observations into the next scientific question.”

A place to grow as a researcher

Dr. Taisei Wakigawa did not begin his career studying mitochondria. As a master’s student at Kobe University, he trained as a licensed physical therapist while studying skeletal muscle. But as his research progressed, he became more interested in a deeper question: how cells orchestrate protein synthesis.

“That curiosity led me to translation research. I wanted to understand it in much greater detail, and ribosome profiling offered exactly that opportunity.”

RIKEN had long been on his radar, but what convinced him to join was not only the institution’s reputation. It was the people.

“What impressed me most when I visited the lab was the atmosphere,” Wakigawa says.

“The students weren’t simply being trained—they were already thinking and discussing science as independent researchers. That was exactly the environment where I wanted to grow.”

Since joining the RNA Systems Biochemistry Laboratory as a Ph.D. student, he has carried out all his research at RIKEN PRI, where he values both the scientific culture and the collaborative environment.

“Everyone here genuinely enjoys research. Students, postdocs, staff scientists, and principal investigators discuss ideas openly, and exciting results quickly become new questions. Collaboration also extends beyond individual laboratories.”

Looking beyond sequencing

Dr. Taisei Wakigawa sees this study not as the end of the story, but as a starting point for a broader investigation of mitochondrial gene expression. Ribosome profiling has given his team a precise view of where translation pauses, down to the level of individual codons.

“But sequencing still gives us only a snapshot. Once the cells are lysed, we lose the spatial and temporal context. I want to understand not only translation itself, but also how it is coordinated with transcription and mitochondrial dynamics.”

His next goal is to combine sequencing with advanced microscopy to capture where and when gene expression is driven within mitochondria. That broader question is rooted in mitochondria’s evolutionary history.

“Mitochondria originated from bacteria about two billion years ago, yet they still maintain their own gene-expression system alongside the nuclear one. Understanding how these two systems work together is the big question I want to keep pursuing.”

Taisei Wakigawa, Mari Mito, Qi Fang, Yuzuru Itoh, Yoichi Shinkai, Shintaro Iwasaki, "Mitochondrial translation termination, recycling, reinitiation, and rescue for in-frame and out-of-frame contexts", Nature Communications, 10.1038/s41467-026-75248-6

Know more about RNA Systems Biochemistry Laboratory: https://iwasakirna.com/