2010 | Marc Robert Fabian, Nahum Sonenberg, and Witold Filipowicz
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression in animals, plants, and protozoa by posttranscriptionally repressing protein synthesis. They typically base-pair with the 3'-untranslated region (3' UTR) of target mRNAs, often through imperfect pairing, with the miRNA's 5'-proximal "seed" region (positions 2–8) playing a key role in specificity. While miRNAs are known to repress translation and induce mRNA deadenylation and decay, recent studies suggest some miRNAs can also activate translation. miRNAs function as ribonucleoprotein complexes (miRISCs), with Argonaute (AGO) and GW182 proteins being key components. AGO proteins, such as AGO2, are involved in both miRNA repression and RNA interference (RNAi), while GW182 proteins are crucial for miRNA-mediated deadenylation and decay. These proteins interact with the mRNA 3' UTR and are enriched in processing bodies (P bodies), which are involved in the storage or degradation of translationally repressed mRNAs. miRNA-mediated repression can be modulated by various factors, and some miRNAs can activate translation, particularly in quiescent cells. The mechanisms of miRNA action are complex, involving interactions with RNA-binding proteins, cellular compartments, and translation factors. miRNAs can also influence mRNA stability through deadenylation and decapping, with the CCR4-NOT1 complex and poly(A)-binding protein (PABP) playing key roles. These processes are conserved across species and are essential for regulating gene expression in eukaryotic cells.MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression in animals, plants, and protozoa by posttranscriptionally repressing protein synthesis. They typically base-pair with the 3'-untranslated region (3' UTR) of target mRNAs, often through imperfect pairing, with the miRNA's 5'-proximal "seed" region (positions 2–8) playing a key role in specificity. While miRNAs are known to repress translation and induce mRNA deadenylation and decay, recent studies suggest some miRNAs can also activate translation. miRNAs function as ribonucleoprotein complexes (miRISCs), with Argonaute (AGO) and GW182 proteins being key components. AGO proteins, such as AGO2, are involved in both miRNA repression and RNA interference (RNAi), while GW182 proteins are crucial for miRNA-mediated deadenylation and decay. These proteins interact with the mRNA 3' UTR and are enriched in processing bodies (P bodies), which are involved in the storage or degradation of translationally repressed mRNAs. miRNA-mediated repression can be modulated by various factors, and some miRNAs can activate translation, particularly in quiescent cells. The mechanisms of miRNA action are complex, involving interactions with RNA-binding proteins, cellular compartments, and translation factors. miRNAs can also influence mRNA stability through deadenylation and decapping, with the CCR4-NOT1 complex and poly(A)-binding protein (PABP) playing key roles. These processes are conserved across species and are essential for regulating gene expression in eukaryotic cells.