Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cells.
Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cells.
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DOI：
10.1038/nbt.1861
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发表时间：
2011-05
影响因子：
46.9
通讯作者：
中科院分区：
文献类型：
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作者：
Regulation of RNA levels is determined through the interplay between RNA production, processing and degradation. However, since most global studies of RNA regulation do not distinguish the separate contributions of these processes, relatively little is known about how they are temporally integrated to determine changes in RNA levels. In particular, while some studies emphasize the role of changes in the rate of transcription, others suggest a prominent involvement of time-varying degradation rates. Here, we combine metabolic labeling of RNA at high temporal resolution with advanced RNA quantification assays and computational modeling to estimate RNA transcription and degradation rates during the model response of immune dendritic cells (DCs) to pathogens. We find that changes in transcription rates determine the majority of temporal changes in RNA levels, but that changes in degradation rate are important for shaping sharp ‘peaked’ responses. Furthermore, transcription rate changes precede corresponding changes in RNA level by a small lag (15-30 min), which is shorter for induced than for repressed genes. We used massively parallel sequencing of the newly-transcribed RNA population – including non-polyadenylated transcripts – to estimate constant RNA degradation and processing rates. We find that temporally constant degradation rates vary significantly between genes and contribute substantially to the observed differences in the dynamic response, and that specific groups of transcripts, mostly cytokines and transcription factors, are undergoing faster mRNA maturation. Our study provides a new quantitative approach to study key steps in the integrative process of RNA regulation.
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影响因子：
9.9
作者：
Amorim, Maria J.;Cotobal, Cristina;Duncan, Caia;Mata, Juan
通讯作者：
Mata, Juan
影响因子：
4.4
作者：
Elkon R;Zlotorynski E;Zeller KI;Agami R
通讯作者：
Agami R
DOI：
10.1126/science.1179050
发表时间：
2009-10-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Amit I;Garber M;Chevrier N;Leite AP;Donner Y;Eisenhaure T;Guttman M;Grenier JK;Li W;Zuk O;Schubert LA;Birditt B;Shay T;Goren A;Zhang X;Smith Z;Deering R;McDonald RC;Cabili M;Bernstein BE;Rinn JL;Meissner A;Root DE;Hacohen N;Regev A
通讯作者：
Regev A
影响因子：
3.1
作者：
Lagarias, JC;Reeds, JA;Wright, PE
通讯作者：
Wright, PE
影响因子：
14.9
作者：
Benson DA;Karsch-Mizrachi I;Lipman DJ;Ostell J;Wheeler DL
通讯作者：
Wheeler DL