Format

Send to

Choose Destination
Mol Cell. 2019 Dec 30. pii: S1097-2765(19)30896-2. doi: 10.1016/j.molcel.2019.12.005. [Epub ahead of print]

The Dynamics of Cytoplasmic mRNA Metabolism.

Author information

1
Howard Hughes Medical Institute, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2
Howard Hughes Medical Institute, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
4
Howard Hughes Medical Institute, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: dbartel@wi.mit.edu.

Abstract

For all but a few mRNAs, the dynamics of metabolism are unknown. Here, we developed an experimental and analytical framework for examining these dynamics for mRNAs from thousands of genes. mRNAs of mouse fibroblasts exit the nucleus with diverse intragenic and intergenic poly(A)-tail lengths. Once in the cytoplasm, they have a broad (1000-fold) range of deadenylation rate constants, which correspond to cytoplasmic lifetimes. Indeed, with few exceptions, degradation appears to occur primarily through deadenylation-linked mechanisms, with little contribution from either endonucleolytic cleavage or deadenylation-independent decapping. Most mRNA molecules degrade only after their tail lengths fall below 25 nt. Decay rate constants of short-tailed mRNAs vary broadly (1000-fold) and are larger for short-tailed mRNAs that have previously undergone more rapid deadenylation. This coupling helps clear rapidly deadenylated mRNAs, enabling the large range in deadenylation rate constants to impart a similarly large range in stabilities.

KEYWORDS:

5-ethynyl uridine; PAL- seq; TAIL-seq; deadenylation rates; decapping rates; mRNA decay rates; mRNA uridylation; metabolic labeling; poly(A)-tail lengths

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center