Involvement of MicroRNA in AU-Rich Element-Mediated mRNA Instability

Qing Jing; Shuang Huang; Sabine Guth; Tyler Zarubin; Andrea Motoyama; Jianming Chen; Franco Di Padova; Sheng Cai Lin; Hermann Gram; Jiahuai Han

doi:10.1016/j.cell.2004.12.038

Involvement of MicroRNA in AU-Rich Element-Mediated mRNA Instability

Qing Jing, Shuang Huang, Sabine Guth, Tyler Zarubin, Andrea Motoyama, Jianming Chen, Franco Di Padova, Sheng Cai Lin, Hermann Gram, Jiahuai Han

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

725 Scopus citations

Abstract

AU-rich elements (AREs) in the 3′ untranslated region (UTR) of unstable mRNAs dictate their degradation. An RNAi-based screen performed in Drosophila S2 cells has revealed that Dicer1, Argonaute1 (Ago1) and Ago2, components involved in microRNA (miRNA) processing and function, are required for the rapid decay of mRNA containing AREs of tumor necrosis factor-α. The requirement for Dicer in the instability of ARE-containing mRNA (ARE-RNA) was confirmed in HeLa cells. We further observed that miR16, a human miRNA containing an UAAAUAUU sequence that is complementary to the ARE sequence, is required for ARE-RNA turnover. The role of miR16 in ARE-RNA decay is sequence-specific and requires the ARE binding protein tristetraprolin (TTP). TTP does not directly bind to miR16 but interacts through association with Ago/eiF2C family members to complex with miR16 and assists in the targeting of ARE. miRNA targeting of ARE, therefore, appears to be an essential step in ARE-mediated mRNA degradation.

Original language	English (US)
Pages (from-to)	623-634
Number of pages	12
Journal	Cell
Volume	120
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2004.12.038
State	Published - Mar 11 2005
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.cell.2004.12.038

Cite this

@article{cda63379877a44b8bbac7d5770a8ed8d,

title = "Involvement of MicroRNA in AU-Rich Element-Mediated mRNA Instability",

abstract = "AU-rich elements (AREs) in the 3′ untranslated region (UTR) of unstable mRNAs dictate their degradation. An RNAi-based screen performed in Drosophila S2 cells has revealed that Dicer1, Argonaute1 (Ago1) and Ago2, components involved in microRNA (miRNA) processing and function, are required for the rapid decay of mRNA containing AREs of tumor necrosis factor-α. The requirement for Dicer in the instability of ARE-containing mRNA (ARE-RNA) was confirmed in HeLa cells. We further observed that miR16, a human miRNA containing an UAAAUAUU sequence that is complementary to the ARE sequence, is required for ARE-RNA turnover. The role of miR16 in ARE-RNA decay is sequence-specific and requires the ARE binding protein tristetraprolin (TTP). TTP does not directly bind to miR16 but interacts through association with Ago/eiF2C family members to complex with miR16 and assists in the targeting of ARE. miRNA targeting of ARE, therefore, appears to be an essential step in ARE-mediated mRNA degradation.",

author = "Qing Jing and Shuang Huang and Sabine Guth and Tyler Zarubin and Andrea Motoyama and Jianming Chen and {Di Padova}, Franco and Lin, {Sheng Cai} and Hermann Gram and Jiahuai Han",

note = "Funding Information: We thank H. Holtmann for IL-6 and IL-8 cDNA, R. Agami for pSuper vector, A. Shyu for pBBB vector, K. Saigo and N. Doi for anti-human Dicer antibody and myc-eif2C2 expression vector, and S. Stanton for critical reading of this manuscript. This work was supported in part by NIH grants CA93926, AI41637, AI054796, and GM67101. Q.J. was supported in part by the National Basic Research Program of China (G20000056905). ",

year = "2005",

month = mar,

day = "11",

doi = "10.1016/j.cell.2004.12.038",

language = "English (US)",

volume = "120",

pages = "623--634",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - Involvement of MicroRNA in AU-Rich Element-Mediated mRNA Instability

AU - Jing, Qing

AU - Huang, Shuang

AU - Guth, Sabine

AU - Zarubin, Tyler

AU - Motoyama, Andrea

AU - Chen, Jianming

AU - Di Padova, Franco

AU - Lin, Sheng Cai

AU - Gram, Hermann

AU - Han, Jiahuai

N1 - Funding Information: We thank H. Holtmann for IL-6 and IL-8 cDNA, R. Agami for pSuper vector, A. Shyu for pBBB vector, K. Saigo and N. Doi for anti-human Dicer antibody and myc-eif2C2 expression vector, and S. Stanton for critical reading of this manuscript. This work was supported in part by NIH grants CA93926, AI41637, AI054796, and GM67101. Q.J. was supported in part by the National Basic Research Program of China (G20000056905).

PY - 2005/3/11

Y1 - 2005/3/11

N2 - AU-rich elements (AREs) in the 3′ untranslated region (UTR) of unstable mRNAs dictate their degradation. An RNAi-based screen performed in Drosophila S2 cells has revealed that Dicer1, Argonaute1 (Ago1) and Ago2, components involved in microRNA (miRNA) processing and function, are required for the rapid decay of mRNA containing AREs of tumor necrosis factor-α. The requirement for Dicer in the instability of ARE-containing mRNA (ARE-RNA) was confirmed in HeLa cells. We further observed that miR16, a human miRNA containing an UAAAUAUU sequence that is complementary to the ARE sequence, is required for ARE-RNA turnover. The role of miR16 in ARE-RNA decay is sequence-specific and requires the ARE binding protein tristetraprolin (TTP). TTP does not directly bind to miR16 but interacts through association with Ago/eiF2C family members to complex with miR16 and assists in the targeting of ARE. miRNA targeting of ARE, therefore, appears to be an essential step in ARE-mediated mRNA degradation.

AB - AU-rich elements (AREs) in the 3′ untranslated region (UTR) of unstable mRNAs dictate their degradation. An RNAi-based screen performed in Drosophila S2 cells has revealed that Dicer1, Argonaute1 (Ago1) and Ago2, components involved in microRNA (miRNA) processing and function, are required for the rapid decay of mRNA containing AREs of tumor necrosis factor-α. The requirement for Dicer in the instability of ARE-containing mRNA (ARE-RNA) was confirmed in HeLa cells. We further observed that miR16, a human miRNA containing an UAAAUAUU sequence that is complementary to the ARE sequence, is required for ARE-RNA turnover. The role of miR16 in ARE-RNA decay is sequence-specific and requires the ARE binding protein tristetraprolin (TTP). TTP does not directly bind to miR16 but interacts through association with Ago/eiF2C family members to complex with miR16 and assists in the targeting of ARE. miRNA targeting of ARE, therefore, appears to be an essential step in ARE-mediated mRNA degradation.

UR - http://www.scopus.com/inward/record.url?scp=20044388720&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20044388720&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2004.12.038

DO - 10.1016/j.cell.2004.12.038

M3 - Article

C2 - 15766526

AN - SCOPUS:20044388720

SN - 0092-8674

VL - 120

SP - 623

EP - 634

JO - Cell

JF - Cell

IS - 5

ER -

Involvement of MicroRNA in AU-Rich Element-Mediated mRNA Instability

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this