Genome-wide kinetic profiling of pre-mRNA 3' end cleavage.

ABSTRACT: Cleavage and polyadenylation is necessary for the formation of mature mRNA molecules. The rate at which this process occurs can determine the temporal availability of mRNA for subsequent function throughout the cell and is likely tightly regulated. Despite advances in high-throughput approaches for global kinetic profiling of RNA maturation, genome-wide 3' end cleavage rates have never been measured. Here, we describe a novel approach to estimate the rates of cleavage, using metabolic labeling of nascent RNA, high-throughput sequencing, and mathematical modeling. Using in silico simulations of nascent RNA-seq data, we show that our approach can accurately and precisely estimate cleavage half-lives for both constitutive and alternative sites. We find that 3' end cleavage is fast on average,

SUBMITTER: Torres-Ulloa L 

PROVIDER: S-EPMC10870368 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature