Recognition of MicroRNA Precursors and Targets

Participants: Wynne Hsu, Coral Lai, Mong Li Lee, Limsoon Wong, Lianghuai Yang, Yun Zheng, Stanley Ng


Background

MicroRNAs (miRNAs) are small non-coding RNAs of about 22 nucleotides long. MicroRNA transcripts, which may be produced by RNA polymerase II or III, often fold to form stem loop structures, and become what are called primary miRNAs, or pri-miRNAs. In the nucleus, the Drosha RNase III endonuclease cleavages both strands of the stem at the base of the primary stem loop, and produce the pre-miRNAs. Then, in cytoplasm, a second RNase III endonuclease, Dicer, together with its dsRNA-binding partner protein makes a second pair of cuts and defines the other end of the mature miRNAs, which produces the miRNA:miRNA* duplex. Finally, the miRNA stand is separated from the duplex by the helicase and forms the mature miRNA molecules. The mature miRNAs are then loaded to RNA-induced silencing complex (RISC), which binds the 3' untranslated region of messenger RNAs of the miRNA target genes to repress the production of related proteins.

MicroRNAs play an important regulatory functions in eukaryotic gene expression through mRNA degradation or translation inhibition. The regulatory functions of miRNAs range from cell proliferation, fat metabolism, neuronal patterning in nematodes, neurological diseases, modulation of hematopoietic lineage differentiation in mammals, development, cell death, cancer, and control of leaf and flower development in plants. An miRNA downregulates the translation of target mRNAs through base-pairing to these target mRNAs. In animals, miRNAs tend to bind to the 3 untranslated region (3 UTR) of their target transcripts to repress translation. The pairing between miRNAs and their target mRNAs usually includes short bulges and/or mismatches. In contrast, in all known cases, plant miRNAs bind to the protein-coding region of their target mRNAs with three or fewer mismatches and induce target mRNA degradation or repress mRNA translation.

Objectives

Selected Publications

Dissertations

Acknowledgements

This project is supported in part by the I2R-SOC Joint Lab on Knowledge Discovery from Clinical Data (7/03 - 6/07), NUS OLS Bioinformatics Programme (Ng, Wong: 7/07-12/07), and an A*STAR AGS scholarship (Ng).


Last updated: 5/4/08, Limsoon Wong.