IMR Press / FBL / Volume 13 / Issue 7 / DOI: 10.2741/2865

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Protein interactions and complexes in human microRNA biogenesis and function
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1 Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHUL-CHUQ, 2705 Blvd Laurier, Quebec, QC, G1V 4G2, Canada, and Faculty of Medicine, Université Laval, Quebec, QC, G1K 7P4, Canada

*Author to whom correspondence should be addressed.

Front. Biosci. (Landmark Ed) 2008, 13(7), 2537–2547;
Published: 1 January 2008

Encoded in the genome of most eukaryotes, microRNAs (miRNAs) have been proposed to regulate specifically up to 90% of human genes through a process known as miRNA-guided RNA silencing. The aim of this review is to present this process as the integration of a succession of specialized molecular machines exerting well defined functions. The nuclear microprocessor complex initially recognizes and processes its primary miRNA substrate into a miRNA precursor (pre-miRNA). This structure is then exported to the cytoplasm by the Exportin-5 complex where it is presented to the pre-miRNA processing complex. Following pre-miRNA conversion into a miRNA:miRNA* duplex, this complex is assembled into a miRNA-containing ribonucleoprotein (miRNP) complex, after which the miRNA strand is selected. The degree of complementarity of the miRNA for its messenger RNA (mRNA) target guides the recruitment of the miRNP complex. Initially repressing its translation, the miRNP-silenced mRNA is directed to the P-bodies, where the mRNA is either released from its inhibition upon a cellular signal and/or actively degraded. The potency and specificity of miRNA biogenesis and function rely on the distinct protein•protein, protein•RNA and RNA:RNA interactions found in different complexes, each of which fulfill a specific function in a well orchestrated process.

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