Elucidation of a C-rich signature motif in target mRNAs of RNA-binding protein TIAR.

Elucidation of a C-rich signature motif in target mRNAs of RNA-binding protein TIAR. Research Abstract Details 

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Elucidation of a C-rich signature motif in target mRNAs of RNA-binding protein TIAR. Abstract Text:

Henry S Kim,Yuki Kuwano,Ming Zhan,Rudolf Pullmann,Krystyna Mazan-Mamczarz,Huai Li,Nancy Kedersha,Paul Anderson,Matthew C J Wilce,Myriam Gorospe,Jacqueline A Wilce,Henry S Kim,Yuki Kuwano,Ming Zhan,Rudolf Pullmann,Krystyna Mazan-Mamczarz,Huai Li,Nancy Kedersha,Paul Anderson,Matthew C J Wilce,Myriam Gorospe,Jacqueline A Wilce,

The RNA-binding protein TIAR (related to TIA-1 [T-cell-restricted intracellular antigen 1]) was shown to associate with subsets of mRNAs bearing U-rich sequences in their 3' untranslated regions. TIAR can function as a translational repressor, particularly in response to cytotoxic agents. Using unstressed colon cancer cells, collections of mRNAs associated with TIAR were isolated by immunoprecipitation (IP) of (TIAR-RNA) ribonucleoprotein (RNP) complexes, identified by microarray analysis, and used to elucidate a common signature motif present among TIAR target transcripts. The predicted TIAR motif was an unexpectedly cytosine-rich, 28- to 32-nucleotide-long element forming a stem and a loop of variable size with an additional side loop. The ability of TIAR to bind an RNA oligonucleotide with a representative C-rich TIAR motif sequence was verified in vitro using surface plasmon resonance. By this analysis, TIAR containing two or three RNA recognition domains (TIAR12 and TIAR123) showed low but significant binding to the C-rich sequence. In vivo, insertion of the C-rich motif into a heterologous reporter strongly suppressed its translation in cultured cells. Using this signature motif, an additional approximately 2,209 UniGene targets were identified (2.0% of the total UniGene database). A subset of specific mRNAs were validated by RNP IP analysis. Interestingly, in response to treatment with short-wavelength UV light (UVC), a stress agent causing DNA damage, each of these target mRNAs bearing C-rich motifs dissociated from TIAR. In turn, expression of the encoded proteins was elevated in a TIAR-dependent manner. In sum, we report the identification of a C-rich signature motif present in TIAR target mRNAs whose association with TIAR decreases following exposure to a stress-causing agent.

Elucidation of a C-rich signature motif in target mRNAs of RNA-binding protein TIAR. Publishing Authors By Initials

HS Kim,Y Kuwano,M Zhan,R Pullmann,K Mazan-Mamczarz,H Li,N Kedersha,P Anderson,MC Wilce,M Gorospe,JA Wilce,HS Kim,Y Kuwano,M Zhan,R Pullmann,K Mazan-Mamczarz,H Li,N Kedersha,P Anderson,MC Wilce,M Gorospe,JA Wilce,

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Elucidation of a C-rich signature motif in target mRNAs of RNA-binding protein TIAR. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular and cellular biology

VOLUME: 27

Page Numbers: 6806-17

Journal Abbreviation: Mol. Cell. Biol.

ISSN: 0270-7306

DAY: 6

MONTH: 08

YEAR: 2007

Elucidation of a C-rich signature motif in target mRNAs of RNA-binding protein TIAR. Information

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LANGUAGE: eng

NlmUniqueID: 8109087

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Grant and Affiliation Information for Elucidation of a C-rich signature motif in target mRNAs of RNA-binding protein TIAR.

AFFILIATION: Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia.

Country: United States

AGENCY: United States NIAID

GRANT: AI33600

ACRONYM: AI

MEDLINETA: Mol Cell Biol

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