LincRNA-p21 Suppresses Target mRNA Translation

Je Hyun Yoon; Kotb Abdelmohsen; Subramanya Srikantan; Xiaoling Yang; Jennifer L. Martindale; Supriyo De; Maite Huarte; Ming Zhan; Kevin G. Becker; Myriam Gorospe

doi:10.1016/j.molcel.2012.06.027

LincRNA-p21 Suppresses Target mRNA Translation

Je Hyun Yoon, Kotb Abdelmohsen, Subramanya Srikantan, Xiaoling Yang, Jennifer L. Martindale, Supriyo De, Maite Huarte, Ming Zhan, Kevin G. Becker, Myriam Gorospe

Academic Institute

Research output: Contribution to journal › Article › peer-review

767 Scopus citations

Abstract

Mammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription. Here we report a posttranscriptional function for lincRNA-p21 as a modulator of translation. Association of the RNA-binding protein HuR with lincRNA-p21 favored the recruitment of let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability. Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma HeLa cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation. With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and β-catenin translation and increased the levels of these proteins. We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels. Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation.

Original language	English (US)
Pages (from-to)	648-655
Number of pages	8
Journal	Molecular Cell
Volume	47
Issue number	4
DOIs	https://doi.org/10.1016/j.molcel.2012.06.027
State	Published - Aug 24 2012

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2012.06.027

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title = "LincRNA-p21 Suppresses Target mRNA Translation",

abstract = "Mammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription. Here we report a posttranscriptional function for lincRNA-p21 as a modulator of translation. Association of the RNA-binding protein HuR with lincRNA-p21 favored the recruitment of let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability. Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma HeLa cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation. With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and β-catenin translation and increased the levels of these proteins. We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels. Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation.",

author = "Yoon, {Je Hyun} and Kotb Abdelmohsen and Subramanya Srikantan and Xiaoling Yang and Martindale, {Jennifer L.} and Supriyo De and Maite Huarte and Ming Zhan and Becker, {Kevin G.} and Myriam Gorospe",

note = "Funding Information: We thank D.L. Kontoyiannis, G.J. Hannon, N. Mukherjee, and J.D. Keene for providing reagents and information. J.-H.Y., K.A., S.S., X.Y., J.L.M., S.D., K.G.B., and M.G. were supported by the NIA-IRP, NIH. M.Z. was supported by NIH U54CA149169. ",

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doi = "10.1016/j.molcel.2012.06.027",

language = "English (US)",

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T1 - LincRNA-p21 Suppresses Target mRNA Translation

AU - Yoon, Je Hyun

AU - Abdelmohsen, Kotb

AU - Srikantan, Subramanya

AU - Yang, Xiaoling

AU - Martindale, Jennifer L.

AU - De, Supriyo

AU - Huarte, Maite

AU - Zhan, Ming

AU - Becker, Kevin G.

AU - Gorospe, Myriam

N1 - Funding Information: We thank D.L. Kontoyiannis, G.J. Hannon, N. Mukherjee, and J.D. Keene for providing reagents and information. J.-H.Y., K.A., S.S., X.Y., J.L.M., S.D., K.G.B., and M.G. were supported by the NIA-IRP, NIH. M.Z. was supported by NIH U54CA149169.

PY - 2012/8/24

Y1 - 2012/8/24

N2 - Mammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription. Here we report a posttranscriptional function for lincRNA-p21 as a modulator of translation. Association of the RNA-binding protein HuR with lincRNA-p21 favored the recruitment of let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability. Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma HeLa cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation. With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and β-catenin translation and increased the levels of these proteins. We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels. Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation.

AB - Mammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription. Here we report a posttranscriptional function for lincRNA-p21 as a modulator of translation. Association of the RNA-binding protein HuR with lincRNA-p21 favored the recruitment of let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability. Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma HeLa cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation. With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and β-catenin translation and increased the levels of these proteins. We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels. Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation.

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LincRNA-p21 Suppresses Target mRNA Translation

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