A whole-genome RNAi Screen for C. elegans miRNA pathway genes.

A whole-genome RNAi Screen for C. elegans miRNA pathway genes. Research Abstract Details 

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A whole-genome RNAi Screen for C. elegans miRNA pathway genes. Abstract Text:

Devin H Parry,Jinling Xu,Gary Ruvkun,Devin H Parry,Jinling Xu,Gary Ruvkun,Devin H Parry,Jinling Xu,Gary Ruvkun,

BACKGROUND: miRNAs are an abundant class of small, endogenous regulatory RNAs. Although it is now appreciated that miRNAs are involved in a broad range of biological processes, relatively little is known about the actual mechanism by which miRNAs downregulate target gene expression. An exploration of which protein cofactors are necessary for a miRNA to downregulate a target gene should reveal more fully the molecular mechanisms by which miRNAs are processed, trafficked, and regulate their target genes. RESULTS: A weak allele of the C. elegans miRNA gene let-7 was used as a sensitized genetic background for a whole-genome RNAi screen to detect miRNA pathway genes, and 213 candidate miRNA pathway genes were identified. About 2/3 of the 61 candidates with the strongest phenotype were validated through genetic tests examining the dependence of the let-7 phenotype on target genes known to function in the let-7 pathway. Biochemical tests for let-7 miRNA production place the function of nearly all of these new miRNA pathway genes downstream of let-7 expression and processing. By monitoring the downregulation of the protein product of the lin-14 mRNA, which is the target of the lin-4 miRNA, we have identified 19 general miRNA pathway genes. CONCLUSIONS: The 213 candidate miRNA pathway genes identified could act at steps that produce and traffic miRNAs or in downstream steps that detect miRNA::mRNA duplexes to regulate mRNA translation. The 19 validated general miRNA pathway genes are good candidates for genes that may define protein cofactors for sorting or targeting miRNA::mRNA duplexes, or for recognizing the miRNA base-paired to the target mRNA to downregulate translation.

A whole-genome RNAi Screen for C. elegans miRNA pathway genes. Publishing Authors By Initials

DH Parry,J Xu,G Ruvkun,DH Parry,J Xu,G Ruvkun,DH Parry,J Xu,G Ruvkun,

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A whole-genome RNAi Screen for C. elegans miRNA pathway genes. Journal Published:

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

Journal: Current biology : CB

VOLUME: 17

Page Numbers: 2013-22

Journal Abbreviation: Curr. Biol.

ISSN: 0960-9822

DAY: 20

MONTH: 11

YEAR: 2007

A whole-genome RNAi Screen for C. elegans miRNA pathway genes. Information

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LANGUAGE: eng

NlmUniqueID: 9107782

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Grant and Affiliation Information for A whole-genome RNAi Screen for C. elegans miRNA pathway genes.

AFFILIATION: Department of Genetics, Harvard Medical School, Richard B. Simches Research Building, 185 Cambridge Street, CPZN-7250, Boston, Massachusetts 02114-2790, USA.

Country: England

AGENCY: United States NIGMS

GRANT: R01-GM44619

ACRONYM: GM

MEDLINETA: Curr Biol

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