Liu, S.J. et al. Science 355, aah7111 (2017).
For a handful of long noncoding RNAs (lncRNAs), their regulatory function is well understood, such as that of XIST for X-chromosome inactivation; but for tens of thousands of other lncRNAs encoded in the human genome, their function remains unknown. Liu et al. now present a large-scale screen based on CRISPR interference (CRISPRi) that systematically inhibits transcription of over 16,000 lncRNAs. With the help of the CRISPR noncoding library (CRiNCL), the researchers discovered 499 lncRNAs that influenced cell growth. Surprisingly, almost 90% of them did so in only one of seven human cell lines. The lncRNAs caused extensive changes in genome-wide expression patterns exclusively in the cell lines they affected. This cell-type-specific action of lncRNAs will be important to consider as their role in development and disease is further elucidated.