Hidden Protein Found in Non-Coding RNA Aids Cell Division

A previously unknown protein hidden inside RNA once classified as non-protein-coding turns out to play a role in helping cells divide correctly, according to new research from the University of Gothenburg. The RNA molecule that produces this protein also carries out a separate function of its own during cell division, and the findings could offer new insight into what goes wrong in diseases such as cancer.

Modern sequencing and protein-analysis technologies have made it possible to uncover a growing “hidden proteome”—proteins encoded by parts of the genome that researchers had previously overlooked. Using these tools, University of Gothenburg researchers identified one such protein, which they named MSEP. It is encoded by an RNA molecule called ARHGEF17-AS1, despite that RNA having previously been classified as non-protein-coding. Both the RNA molecule and MSEP help maintain the cellular machinery responsible for pulling chromosomes apart when a cell divides.

“What is particularly interesting is that the RNA molecule and the protein do not perform the same job,” says Sagar Mahale, first author of both studies describing the work. “They act through different pathways in the cell, but both help maintain the same essential structure when the cell divides.” In two studies published in Cell Reports, the researchers targeted the RNA molecule and MSEP production separately in cultured cells, allowing them to tell the two functions apart.

Because cancer cells rely on successful cell division to multiply, the team also examined the RNA molecule and MSEP in cancer cells. MSEP levels turned out to be higher in the cancer cell lines they studied than in normal cell lines. When the researchers reduced the amount of RNA or disrupted MSEP production in cultured cervical cancer cells, the cells showed reduced growth and proliferation. 

“These findings raise the question of whether certain tumors are particularly dependent on MSEP to continue dividing,” says Chandrasekhar Kanduri, senior author of both studies. “But it is too early to say whether the protein could become a target for future treatments.”

The findings are based on studies of cultured cells, and the researchers say further work is needed to determine what roles the RNA molecule and MSEP play in tumors and other tissues.