NYC Gazette

Researchers at New York University and the New York Genome Center have made significant strides in understanding noncoding RNAs, often previously dismissed as "junk" DNA. Using a CRISPR technology variant that targets RNA rather than DNA, the team discovered nearly 800 noncoding RNAs crucial for various human cell functions.

"This survey of functional noncoding RNAs advances our understanding of the human genome and demonstrates the potential of CRISPR screens that specifically target RNA—even those that don’t code for proteins," stated Neville Sanjana, an associate professor at NYU and senior author of the study published in Cell.

The innovative approach employs Cas13 enzyme technology to target RNA without affecting nearby protein-coding genes. This differs from traditional CRISPR methods that use Cas9 to edit DNA directly. The research systematically analyzed 6,200 gene pairs across five different human cell lines using this method.

Simon Müller, co-first author and postdoctoral associate in Sanjana's lab, highlighted a critical question: "We now have this technology, but the biological question still remains: which parts of the noncoding genome are actually functional?"

Their findings revealed 778 essential long noncoding RNAs (lncRNAs), including a core group universally essential across cell types and others with specific functions depending on the cell type. Interestingly, most essential lncRNAs operate independently of adjacent protein-coding genes.

Wen-Wei Liang, another co-first author from Sanjana’s lab, emphasized their importance: "With Cas13, we can specifically ask, ‘What are the functions of those transcripts?’ They are not junk—we found that they are really important and essential to cells growing and dividing."

The study also noted that many essential lncRNAs play roles in key pathways related to cell proliferation—a process vital for both development and cancer progression. Analysis of around 9,000 tumors showed altered expression levels of certain lncRNAs associated with cancer survival rates.

Sanjana added insights into potential medical applications: "These noncoding RNAs may yield new biomarkers and therapeutic targets for cancer treatment, a potential opportunity for personalized medicine given their cell type-specific expression."

Additional contributors to this research include Sydney Hart, Hans-Hermann Wessels, Alejandro Méndez-Mancilla among others from NYU and the New York Genome Center. The study received funding support from various institutes including the National Human Genome Research Institute and National Cancer Institute.