MicroRNA function: multiple mechanisms for a tiny RNA?

Abstract

MicroRNAs are sequence-specific regulators of post-transcriptional gene expression in many eukaryotes. They are believed to control the expression of thousands of target mRNAs, with each mRNA believed to be targeted by multiple microRNAs. Recent studies have uncovered various mechanisms by which microRNAs down-regulate their target mRNAs and have linked a well-known subcellular structure, the cytoplasmic processing bodies (PBs) to the microRNA pathway. The finding that microRNAs are misexpressed in cancers has reinforced the idea that their regulatory roles are very important.

FIGURE 1.

Models of miRNA function. The two-step model: Upon binding to the 3′-UTR of a target mRNA, the miRNP complex inhibits translation initiation, presumably by interfering with the 7mG cap function in recruiting eIF4E. Next, the repressed mRNA:miRNP complex is moved to the P-bodies (PBs) for storage. It is speculated that there are separate compartments for storage of the repressed mRNA and for the core PB components such as Dcp1, Xrn1, etc. It is possible that a part of the stored mRNA is degraded via decapping or that once repression is released, they exit the PBs and re-enter translation. One-step model: Binding of the miRNP to the target mRNA directs the mRNA to the PBs. Disassembly of ribosomes on the message occurs prior to entry into the PBs. The mRNA can then be either degraded or stored for later reuse. 7mG, 7-methyl guanine; AAAA, polyadenosine tail; 4E, eIF4E; 4G, eIF4G.