Novel RNA molecule may influence patient survival in certain blood cancers

In a recent study published in the Proceedings of the National Academy of Sciences (PNAS), researchers at the Texas A&M University Health Science Center (Texas A&M Health) identify a novel RNA molecule that plays a crucial role in preserving the integrity of a key cellular structure, nucleolus (a dense region of the cell containing a subset of crucial genetic material). Their findings also suggest this molecule may influence patient survival in certain blood cancers.

A surprising discovery inside a familiar gene

RNA, or ribonucleic acid, is a short-lived molecule copied from DNA that enables cells to use genetic information. Specific DNA sequences are copied into RNA, which then delivers these instructions to the cellular machinery responsible for making proteins. Through this process, RNA acts as the go-between, translating DNA's blueprints into real-time cellular activity.

This research reveals an RNA molecule that regulates key cellular functions without turning into protein, thus functioning as a "non-coding" RNA.

The laboratory of Dr. Irtisha Singh at the Texas A&M Naresh K. Vashisht College of Medicine identified a novel non-coding RNA they named CUL1-IPA that originates from the well-characterized CUL1 protein-coding gene. Unlike the canonical RNA that produces the CUL1 protein, this newly discovered RNA stays in the nucleus. Instead, it performs a completely different cellular function, supporting the structural integrity and activity of the nucleolus, the essential center for ribosome production.

"This finding redefines the conventional assumption that protein-coding genes produce only protein-related messages," said Singh, senior author of the study.

When researchers removed CUL1-IPA from living cells, they observed dramatic effects: The nucleolus (a dense region of the cell containing subset of crucial genetic material) broke apart, and the cells displayed signs of stress.

"We were amazed at how essential this RNA turned out to be," said Dr. Sumana Mallick, co-first author of the study. "Removing it caused the nucleolus to lose its structural integrity, making it clear that non-coding RNAs from protein-coding genes can play central regulatory roles."

A link to cancer patient outcomes

This discovery goes beyond basic biology. The Singh Lab analyzed patient data from two types of blood cancers: multiple myeloma and chronic lymphocytic leukemia. They found that patients with more severe forms of these cancers had higher levels of CUL1-IPA, regardless of how much of the traditional CUL1 RNA was present.

"Its expression correlates with patient survival in blood cancers and may contribute to how aggressive these cancers become," said Dr. Pranita Borkar, co-first author of the article.

Because cancer cells depend on robust ribosome production for rapid growth, regulatory RNAs that support nucleolar function may inadvertently aid tumor progression, making molecules like CUL1-IPA potential biomarkers or therapeutic targets.

Rethinking how genes work

The discovery of CUL1-IPA adds to a growing body of evidence that genes are more versatile than once believed. A single gene can produce multiple RNA molecules, each with its own distinct function, some of which may play major roles in health and disease.

Molecules such as CUL1-IPA may ultimately be used as biomarkers to guide cancer treatment decisions, or even serve as targets for future therapies, opening the door to a whole new field of possible anti-cancer medications.

The study was supported by grants from the National Institutes of Health, the Cancer Prevention and Research Institute of Texas (CPRIT) and Texas A&M Health, along with additional internal funding that supports early-stage scientific discovery.