GSBS Student Publications

Student Author(s)

Megha Ghildiyal

GSBS Program

Interdisciplinary Graduate Program

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Program in Bioinformatics and Integrative Biology

Date

1-2010

Document Type

Article

Medical Subject Headings

MicroRNAs; RNA, Small Interfering; Drosophila Proteins; RNA-Induced Silencing Complex; RNA Interference

Disciplines

Biochemistry | Genetics | Molecular Biology | Molecular Genetics

Abstract

In flies, small silencing RNAs are sorted between Argonaute1 (Ago1), the central protein component of the microRNA (miRNA) pathway, and Argonaute2 (Ago2), which mediates RNA interference. Extensive double-stranded character-as is found in small interfering RNAs (siRNAs)-directs duplexes into Ago2, whereas central mismatches, like those found in miRNA/miRNA* duplexes, direct duplexes into Ago1. Central to this sorting decision is the affinity of the small RNA duplex for the Dcr-2/R2D2 heterodimer, which loads small RNAs into Ago2. Here, we show that while most Drosophila miRNAs are bound to Ago1, miRNA* strands accumulate bound to Ago2. Like siRNA loading, efficient loading of miRNA* strands in Ago2 favors duplexes with a paired central region and requires both Dcr-2 and R2D2. Those miRNA and miRNA* sequences bound to Ago2, like siRNAs diced in vivo from long double-stranded RNA, typically begin with cytidine, whereas Ago1-bound miRNA and miRNA* disproportionately begin with uridine. Consequently, some pre-miRNA generate two or more isoforms from the same side of the stem that differentially partition between Ago1 and Ago2. Our findings provide the first genome-wide test for the idea that Drosophila small RNAs are sorted between Ago1 and Ago2 according to their duplex structure and the identity of their first nucleotide.

Rights and Permissions

Citation: Ghildiyal M, Xu J, Seitz H, Weng Z, Zamore PD. Sorting of Drosophila small silencing RNAs partitions microRNA* strands into the RNA interference pathway. RNA. 2010 Jan;16(1):43-56. doi: 10.1261/rna.1972910. Epub 2009 Nov 16. PubMed PMID: 19917635; PubMed Central PMCID: PMC2802036. Link to article on publisher's website.

Comments

Freely available online through the RNA Open Access option.

Related Resources

Link to article in PubMed

Keywords

microRNA, miRNA, siRNA, Argonaute, RNA interference, RNAi, small RNA sorting

Journal Title

RNA (New York, N.Y.)

PubMed ID

19917635

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