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Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals

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Tani, Hidenori, Mizutani, Rena, Salam, Kazi Abdus, Tano, Keiko, Ijiri, Kenichi, Wakamatsu, Ai, Isogai, Takao, Suzuki, Yutaka, Akimitsu, Nobuyoshi·2012·Genome Research

DOI 10.1101/gr.130559.111

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Abstract

Mammalian genomes produce huge numbers of noncoding RNAs (ncRNAs). However, the functions of most ncRNAs are unclear, and novel techniques that can distinguish functional ncRNAs are needed. Studies of mRNAs have revealed that the half-life of each mRNA is closely related to its physiological function, raising the possibility that the RNA stability of an ncRNA reflects its function. In this study, we first determined the half-lives of 11,052 mRNAs and 1418 ncRNAs in HeLa Tet-off (TO) cells by developing a novel genome-wide method, which we named 5′-br omo-uridine i mmunoprecipitation c hase–deep sequencing analysis (BRIC-seq). This method involved pulse-labeling endogenous RNAs with 5′-bromo-uridine and measuring the ongoing decrease in RNA levels over time using multifaceted deep sequencing. By analyzing the relationship between RNA half-lives and functional categories, we found that RNAs with a long half-life (t1/2 ≥ 4 h) contained a significant proportion of ncRNAs, as well as mRNAs involved in housekeeping functions, whereas RNAs with a short half-life (t1/2 < 4 h) included known regulatory ncRNAs and regulatory mRNAs. The stabilities of a significant set of short-lived ncRNAs are regulated by external stimuli, such as retinoic acid treatment. In particular, we identified and characterized several novel long ncRNAs involved in cell proliferation from the group of short-lived ncRNAs. We designated this novel class of ncRNAs with a short half-life as S hort-Li ved noncoding T ranscripts (SLiTs). We propose that the strategy of monitoring RNA half-life will provide a powerful tool for investigating hitherto functionally uncharacterized regulatory RNAs.

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Authors: Tani, H., Mizutani, R., Salam, K. A., Tano, K., Ijiri, K., Wakamatsu, A., Isogai, T., Suzuki, Y., & Akimitsu, N.
Venue: Genome Research
Publisher: Cold Spring Harbor Laboratory
Published: 2012-02-27
Volume: 22
Issue: 5
Pages: 947-956
ISSN: 1088-9051 (ISSN-L)
DOI: 10.1101/gr.130559.111
OpenAlex: W2136086657
Cited by: 464
References: 8
Type: posted content
Language: en
Open access: bronze

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Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals

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