The RNA degradation pathway regulates the function of GAS5 a non-coding RNA in mammalian cells.

Studies of various mRNAs have revealed that changes in the abundance of transcripts, through mRNA degradation, act as a critical step in the control of various biological pathways. Similarly, the regulation of non-coding RNA (ncRNA) levels is also considered to be important for their biological func...

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Autores principales: Hidenori Tani, Masaki Torimura, Nobuyoshi Akimitsu
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:3bc8c3595f9142ab828e2a045e59088d2021-11-18T07:59:21ZThe RNA degradation pathway regulates the function of GAS5 a non-coding RNA in mammalian cells.1932-620310.1371/journal.pone.0055684https://doaj.org/article/3bc8c3595f9142ab828e2a045e59088d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23383264/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Studies of various mRNAs have revealed that changes in the abundance of transcripts, through mRNA degradation, act as a critical step in the control of various biological pathways. Similarly, the regulation of non-coding RNA (ncRNA) levels is also considered to be important for their biological functions; however, far less is known about the mechanisms and biological importance of ncRNA turnover for the regulation of ncRNA functions. The growth arrest-specific 5 (GAS5) ncRNA accumulates during growth arrest induced by serum starvation and its transcript is degraded by the well characterized nonsense-mediated RNA decay (NMD) pathway. Historically, NMD was discovered as a RNA quality control system to eliminate aberrant transcripts; however, accumulating evidence shows that NMD also regulates the abundance of physiological transcripts. Interestingly, the GAS5 transcript has the ability to bind the glucocorticoid receptor (GR), resulting in the inhibition of its ligand-dependent association with DNA. The GR binds the promoters of various glucocorticoid-responsive genes, including apoptosis-related genes. In this study, we examined whether the RNA degradation pathway can regulate this function of GAS5. We measured the steady-state abundance and the decay rate of GAS5 in UPF1-depleted human cells using the 5'-bromo-uridine immunoprecipitation chase (BRIC) method, an inhibitor-free method for directly measuring RNA stability. We found that levels of the GAS5 transcript were elevated owing to prolonged decay rates in response to UPF1 depletion, and consequently the apoptosis-related genes, cIAP2 and SGK1, were down-regulated. In addition, serum starvation also increased the transcript levels of GAS5 because of prolonged decay rates, and conversely decreased levels of cIAP2 and SGK1 mRNA. Taken together, we found that the RNA degradation pathway can regulate the function of the GAS5 ncRNA in mammalian cells.Hidenori TaniMasaki TorimuraNobuyoshi AkimitsuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e55684 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Hidenori Tani
Masaki Torimura
Nobuyoshi Akimitsu
The RNA degradation pathway regulates the function of GAS5 a non-coding RNA in mammalian cells.
description Studies of various mRNAs have revealed that changes in the abundance of transcripts, through mRNA degradation, act as a critical step in the control of various biological pathways. Similarly, the regulation of non-coding RNA (ncRNA) levels is also considered to be important for their biological functions; however, far less is known about the mechanisms and biological importance of ncRNA turnover for the regulation of ncRNA functions. The growth arrest-specific 5 (GAS5) ncRNA accumulates during growth arrest induced by serum starvation and its transcript is degraded by the well characterized nonsense-mediated RNA decay (NMD) pathway. Historically, NMD was discovered as a RNA quality control system to eliminate aberrant transcripts; however, accumulating evidence shows that NMD also regulates the abundance of physiological transcripts. Interestingly, the GAS5 transcript has the ability to bind the glucocorticoid receptor (GR), resulting in the inhibition of its ligand-dependent association with DNA. The GR binds the promoters of various glucocorticoid-responsive genes, including apoptosis-related genes. In this study, we examined whether the RNA degradation pathway can regulate this function of GAS5. We measured the steady-state abundance and the decay rate of GAS5 in UPF1-depleted human cells using the 5'-bromo-uridine immunoprecipitation chase (BRIC) method, an inhibitor-free method for directly measuring RNA stability. We found that levels of the GAS5 transcript were elevated owing to prolonged decay rates in response to UPF1 depletion, and consequently the apoptosis-related genes, cIAP2 and SGK1, were down-regulated. In addition, serum starvation also increased the transcript levels of GAS5 because of prolonged decay rates, and conversely decreased levels of cIAP2 and SGK1 mRNA. Taken together, we found that the RNA degradation pathway can regulate the function of the GAS5 ncRNA in mammalian cells.
format article
author Hidenori Tani
Masaki Torimura
Nobuyoshi Akimitsu
author_facet Hidenori Tani
Masaki Torimura
Nobuyoshi Akimitsu
author_sort Hidenori Tani
title The RNA degradation pathway regulates the function of GAS5 a non-coding RNA in mammalian cells.
title_short The RNA degradation pathway regulates the function of GAS5 a non-coding RNA in mammalian cells.
title_full The RNA degradation pathway regulates the function of GAS5 a non-coding RNA in mammalian cells.
title_fullStr The RNA degradation pathway regulates the function of GAS5 a non-coding RNA in mammalian cells.
title_full_unstemmed The RNA degradation pathway regulates the function of GAS5 a non-coding RNA in mammalian cells.
title_sort rna degradation pathway regulates the function of gas5 a non-coding rna in mammalian cells.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/3bc8c3595f9142ab828e2a045e59088d
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