Ribosomal frameshifting in the CCR5 mRNA is regulated by miRNAs and the NMD pathway.

Belew, Ashton Trey; Meskauskas, Arturas; Musalgaonkar, Sharmishtha; Advani, Vivek M; Sulima, Sergey O; Kasprzak, Wojciech K; Shapiro, Bruce A; Dinman, Jonathan D

Belew, Ashton Trey; Meskauskas, Arturas; Musalgaonkar, Sharmishtha; Advani, Vivek M; Sulima, Sergey O; Kasprzak, Wojciech K; Shapiro, Bruce A; Dinman, Jonathan D.

Afiliação

Belew AT; 1] Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA [2].
Meskauskas A; 1] Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA [2] Department of Biotechnology and Microbiology, Vilnius University, Vilnius, LT 03101, Lithuania [3].
Musalgaonkar S; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA.
Advani VM; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA.
Sulima SO; 1] Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA [2] VIB Center for the Biology of Disease, KU Leuven, Campus Gasthuisberg, Herestraat 49, bus 602, 3000 Leuven, Belgium.
Kasprzak WK; Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
Shapiro BA; Basic Research Laboratory, National Cancer Institute, Frederick, Maryland 21702, USA.
Dinman JD; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA.

Nature ; 512(7514): 265-9, 2014 Aug 21.

Article em En | MEDLINE | ID: mdl-25043019

ABSTRACT

ABSTRACT

Programmed -1 ribosomal frameshift (-1 PRF) signals redirect translating ribosomes to slip back one base on messenger RNAs. Although well characterized in viruses, how these elements may regulate cellular gene expression is not understood. Here we describe a -1 PRF signal in the human mRNA encoding CCR5, the HIV-1 co-receptor. CCR5 mRNA-mediated -1 PRF is directed by an mRNA pseudoknot, and is stimulated by at least two microRNAs. Mapping the mRNA-miRNA interaction suggests that formation of a triplex RNA structure stimulates -1 PRF. A -1 PRF event on the CCR5 mRNA directs translating ribosomes to a premature termination codon, destabilizing it through the nonsense-mediated mRNA decay pathway. At least one additional mRNA decay pathway is also involved. Functional -1 PRF signals that seem to be regulated by miRNAs are also demonstrated in mRNAs encoding six other cytokine receptors, suggesting a novel mode through which immune responses may be fine-tuned in mammalian cells.

Assuntos

Mudança da Fase de Leitura do Gene Ribossômico/genética; MicroRNAs/genética; Degradação do RNAm Mediada por Códon sem Sentido; RNA Mensageiro/genética; RNA Mensageiro/metabolismo; Receptores CCR5/genética; Sequência de Aminoácidos; Sequência de Bases; Sítios de Ligação; Sobrevivência Celular; Códon sem Sentido/genética; Células HeLa; Humanos; Modelos Moleculares; Dados de Sequência Molecular; Conformação de Ácido Nucleico; RNA Mensageiro/química; Receptores de Interleucina/genética; Sequências Reguladoras de Ácido Ribonucleico; Ribossomos/metabolismo

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Texto completo: 1 Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Mudança da Fase de Leitura do Gene Ribossômico / Receptores CCR5 / MicroRNAs / Degradação do RNAm Mediada por Códon sem Sentido Idioma: En Ano de publicação: 2014 Tipo de documento: Article

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