期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：15
页码：8225-8227
DOI：10.1073/pnas.2003702117
出版社：The National Academy of Sciences of the United States of America
摘要：The human genome contains more than 3 billion base pairs, and some estimates suggest that nearly 75% of the genome may be transcribed (1), yet only a small fraction (1 to 2%) of the genome that encodes for protein coding regions has been systematically probed for function. The transcribed genome consists of both short noncoding RNAs (ncRNAs) and long ncRNAs (lncRNAs). The lncRNAs are defined as being greater than 200 nucleotides in length and may be capped, polyadenylated, and spliced like protein-coding genes. By definition, lncRNAs do not contain open reading frames of greater than 50 amino acids, but recent work has uncovered a new world of smaller “microproteins” that are encoded by lncRNAs (2). Other functions of lncRNAs include their ability to form aptamers, which bind and regulate protein complexes (3). The lncRNAs can modulate gene expression by enhancer trapping (4), and by recruiting histone modifiers to chromatin (5, 6). These examples notwithstanding, the function of most lncRNAs is unknown. In PNAS, Raffeiner et al. (7) develop CRISPR-based technology to silence the expression of lncRNAs, and use their technology to identify functional lncRNAs that are regulated by the oncogene MYC. Recent efforts to identify functional lncRNAs have relied on CRISPR technology, which can exquisitely target CRISPR-associated (Cas) proteins to specific genomic locations. This technology has ushered in a new era of functional genomics in which large-scale screens have exponentially increased our understanding of complex genotype−phenotype relationships (8⇓–10). CRISPR-Cas9 pooled screens have become a mainstay of cancer research (11, 12), revealing gene essentiality, synthetic lethality, and mechanisms of resistance to targeted therapy and immunotherapy, among countless other phenotypes. Most of these screens have relied on Cas9-induced DNA double-stranded … [↵][1]1To whom correspondence may be addressed. Email: lstaudt{at}mail.nih.gov. [1]: #xref-corresp-1-1
