Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cells
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Author(s)
Rabani, Michal
Levin, Joshua Z.
Fan, Lin
Adiconis, Xian
Raychowdhury, Raktima
Garber, Manuel
Gnirke, Andreas
Nusbaum, Chad
Hacohen, Nir
Friedman, Nir
Date Issued
April 2011
Journal
Nature Biotechnology
Publisher
Nature Publishing Group
Citation
Rabani, Michal et al. “Metabolic Labeling of RNA Uncovers Principles of RNA Production and Degradation Dynamics in Mammalian Cells.” Nature Biotechnology 29.5 (2011): 436–442. Web.
Version
Author's final manuscript
Abstract
Cellular RNA levels are determined by the interplay of RNA production, processing and degradation. However, because most studies of RNA regulation do not distinguish the separate contributions of these processes, little is known about how they are temporally integrated. Here we combine metabolic labeling of RNA at high temporal resolution with advanced RNA quantification and computational modeling to estimate RNA transcription and degradation rates during the response of mouse dendritic cells to lipopolysaccharide. We find that changes in transcription rates determine the majority of temporal changes in RNA levels, but that changes in degradation rates are important for shaping sharp 'peaked' responses. We used sequencing of the newly transcribed RNA population to estimate temporally constant RNA processing and degradation rates genome wide. Degradation rates vary significantly between genes and contribute to the observed differences in the dynamic response. Certain transcripts, including those encoding cytokines and transcription factors, mature faster. Our study provides a quantitative approach to study the integrative process of RNA regulation.
Description
available in PMC 2011 November 01.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1038/nbt.1861
