Protein interactions and complexes in human microRNA biogenesis and function.
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 x protein, protein x RNA and RNA:RNA interactions found in different complexes, each of which fulfill a specific function in a well orchestrated process.
Perron
Marjorie P
MP
Centre de Recherche du CHUL-CHUQ, 2705 Blvd Laurier, Quebec, QC, G1V 4G2, Canada.
Provost
Patrick
P
D000818:Animals; D060565:Argonaute Proteins; D004062:DiGeorge Syndrome / Q000235:genetics; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D035683:MicroRNAs / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D025941:Protein Interaction Mapping; D011506:Proteins / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D000099253:Trans-Activation Responsive RNA-Binding Protein
D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; D028884:Karyopherins; D035683:MicroRNAs; D011506:Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D043244:Ribonuclease III; D000099253:Trans-Activation Responsive RNA-Binding Protein; C466422:AGO2 protein, human; C446511:XPO5 protein, human