Abstract
Post-transcriptional cleavage and polyadenylation of messenger and long noncoding RNAs is coordinated by a supercomplex of ~20 individual proteins within the eukaryotic nucleus. Polyadenylation plays an essential role in controlling RNA transcript stability, nuclear export, and translation efficiency. More than half of all human RNA transcripts contain multiple polyadenylation signal sequences that can undergo alternative cleavage and polyadenylation during development and cellular differentiation. Alternative cleavage and polyadenylation is an important mechanism for the control of gene expression and defects in 3-prime end processing can give rise to myriad human diseases. Here we show that fusion of catalytically dead Cas13 to a single mammalian polyadenylation factor, Nudix hydrolase 21 (NUDT21), allows for site-specific CRISPR-Cas13-guided cleavage and polyadenylation of RNA in mammalian cells. This approach, which we named Postscriptr, can be utilized for the non-genomic manipulation of gene expression and may have potential future therapeutic applications for treating human RNA processing diseases.
