Unlocking the Cell's 'Gatekeeper': UC Irvine Researchers Discover Critical RNA Quality-Control Factor, LENG8

Irvine, Calif., March 25, 2026 — How do cells ensure that the "blueprints" of genetic information-RNA are accurate and intact before they are exported from the nucleus to the cytoplasm for protein production? A study led by Professor Yongsheng Shi’s team at the University of California, Irvine, recently published in the journal Molecular Cell, has unveiled a previously undefined key mechanism within the cell: the LENG8 protein.

This research not only identifies LENG8 as an evolutionarily highly conserved "gatekeeper" of RNA quality control, but also clarifies how it monitors the processing status of RNA, determining which RNAs can be safely exported, and which must be retained in the nucleus — or even degraded.

In eukaryotes, the production of mRNA is a complex process. If RNA is improperly processed, such as through intron retention or erroneous cleavage, these aberrant RNAs could cause harmful protein expression if allowed to enter the cytoplasm. Consequently, cells have evolved surveillance mechanisms to intercept these defective RNA molecules within the nucleus and ultimately degrade them. However, the specific executors responsible for this interception and degradation have long remained a mystery.

“Using genome-wide CRISPR screening and RNA pull-down assays, we successfully locked onto LENG8 and verify LENG8 is a highly conserved 'gatekeeper' of RNA quality control,” says the study’s first author Lusong Tian, PhD, working with Dr. Yongsheng Shi's laboratory in the Department of Microbiology & Molecular Genetics at UC Irvine's School of Medicine.

LENG8 binds with PCID2 and SEM1 proteins to form a complex named "REX" (RNA Export-suppressing complex). This complex is highly conserved throughout evolution, from yeast to humans. By acting as a "dominant-negative factor," the REX complex interferes with the cell’s core export machinery, TREX-2, physically preventing improperly processed RNA from escaping the nucleus.

In addition, LENG8 does not merely "detain" defective RNA, it also ensures its removal. By interacting with the nuclear exosome adapter PAXT, LENG8 directs these illegitimate RNAs to the nuclear degradation system, effectively eliminating the potential threat.

"This study provides fundamental insights into how cells monitor RNA processing status," the research team noted in the paper. The discovery of LENG8 explains why only correctly processed RNA is granted permission for export.

This research not only expands our understanding of cellular RNA surveillance systems but also opens new avenues for future investigation into the disease mechanisms associated with dysregulated gene expression.

This work was supported by the National Institutes of Health under awards R35GM149294, R01CA297834, DP2GM149554; a Hewitt Foundation Postdoctoral Fellowship; and the Washington Research Foundation Postdoctoral Fellowship. Additional support was provided by UCI core facilities funded by P30CA062203, CA-62203, and NIH-S10OD032327-01.

About the UC Irvine School of Medicine: Each year, the UC Irvine School of Medicine educates more than 500 medical students and over 180 PhD and MS students. Nearly 900 residents and fellows are trained at the UCI Medical Center and affiliated institutions. The School of Medicine offers multiple MD, PhD and MS degrees, and students are encouraged to pursue an expansive range of interests and options. The UC Irvine School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit medschool.uci.edu.