A fourth type of RNA in the cell is microRNA (miRNA). miRNA are short (21 to 23 nucleotides) single-stranded RNA fragments that regulate gene expression (Figure 1). The miRNAs are encoded from the transcribed DNA of genes, but they are not translated into proteins and are therefore often called noncoding RNA. The miRNAs are processed by the cell into molecules that are complementary to mRNA and act to decrease gene expression. Generation of miRNAs involves special processing of longer primary precursor RNAs called pri-miRNAs, which are the primary transcripts of the gene. The pri-miRNAs are then processed in the cell nucleus by the microprocessor complex to pre-miRNAs, which are 70-nucleotide stem-loop structures. These pre-miRNAs are then further processed in the cytoplasm by a specific dicer enzyme that helps assemble an RNA-induced silencing complex (RISC) and generates miRNAs.
Fig1. Regulation of gene expression by microRNA (miRNA). Primary miRNA (pri-miRNA), the primary transcripts of a gene processed in the cell nucleus by the microprocessor complex, are con verted to pre-miRNAs. These pre-miRNAs are then further processed in the cytoplasm by dicer, an enzyme that helps assemble an RNA induced silencing complex (RISC) and generates miRNAs. The miRNAs regulate gene expression by binding to the complementary region of the RNA and repressing translation or promoting degradation of the messenger RNA (mRNA) before it can be translated by the ribosome.
The miRNAs regulate gene expression by binding to the complementary region of the RNA and promoting repression of translation or degradation of the mRNA before it can be translated by the ribosome. miRNAs are believed to play an important role in the normal regulation of cell function, and alterations in miRNA function have been associated with diseases such as cancer and heart disease.
Another type of miRNA is small interfering RNA (siRNA), also called silencing RNA or short interfering RNA. The siRNAs are short, double-stranded RNA molecules, 20 to 25 nucleotides in length, that interfere with the expression of specific genes. siRNAs generally refer to synthetic miRNAs and can be administered to silence expression of specific genes. They are designed to avoid the nuclear processing by the microprocessor complex, and after the siRNA enters the cytoplasm it activates the RISC silencing complex, blocking the translation of mRNA. Because siRNAs can be tailored for any specific sequence in the gene, they can be used to block translation of any mRNA and therefore expression by any gene for which the nucleotide sequence is known. Researchers have proposed that siRNAs may become useful therapeutic tools to silence genes that contribute to the pathophysiology of diseases.
