bi0c00069_si_002.pdf (3.67 MB)
Global Profiling of Cellular Substrates of Human Dcp2
journal contribution
posted on 2020-05-15, 00:14 authored by Yang Luo, Jeremy A. Schofield, Matthew D. Simon, Sarah A. SlavoffDecapping
is the first committed step in 5′-to-3′
RNA decay, and in the cytoplasm of human cells, multiple decapping
enzymes regulate the stabilities of distinct subsets of cellular transcripts.
However, the complete set of RNAs regulated by any individual decapping
enzyme remains incompletely mapped, and no consensus sequence or property
is currently known to unambiguously predict decapping enzyme substrates.
Dcp2 was the first-identified and best-studied eukaryotic decapping
enzyme, but it has been shown to regulate the stability of <400
transcripts in mammalian cells to date. Here, we globally profile
changes in the stability of the human transcriptome in Dcp2 knockout
cells via TimeLapse-seq. We find that P-body enrichment is the strongest
correlate of Dcp2-dependent decay and that modification with m6A exhibits an additive effect with P-body enrichment for Dcp2
targeting. These results are consistent with a model in which P-bodies
represent sites where translationally repressed transcripts are sorted
for decay by soluble cytoplasmic decay complexes through additional
molecular marks.