Biology » Gene Expression » Eukaryotic Post-transcriptional Gene Regulation

Control of RNA Stability

Control of RNA Stability

Before the mRNA leaves the nucleus, it is given two protective “caps” that prevent the end of the strand from degrading during its journey. The 5′ cap, which is placed on the 5′ end of the mRNA, is usually composed of a methylated guanosine triphosphate molecule (GTP). The poly-A tail, which is attached to the 3′ end, is usually composed of a series of adenine nucleotides. Once the RNA is transported to the cytoplasm, the length of time that the RNA resides there can be controlled.

Each RNA molecule has a defined lifespan and decays at a specific rate. This rate of decay can influence how much protein is in the cell. If the decay rate is increased, the RNA will not exist in the cytoplasm as long, shortening the time for translation to occur. Conversely, if the rate of decay is decreased, the RNA molecule will reside in the cytoplasm longer and more protein can be translated. This rate of decay is referred to as the RNA stability. If the RNA is stable, it will be detected for longer periods of time in the cytoplasm.

Binding of proteins to the RNA can influence its stability. Proteins, called RNA-binding proteins, or RBPs, can bind to the regions of the RNA just upstream or downstream of the protein-coding region. These regions in the RNA that are not translated into protein are called the untranslated regions, or UTRs. They are not introns (those have been removed in the nucleus).

Rather, these are regions that regulate mRNA localization, stability, and protein translation. The region just before the protein-coding region is called the 5′ UTR, whereas the region after the coding region is called the 3′ UTR (see the figure below). The binding of RBPs to these regions can increase or decrease the stability of an RNA molecule, depending on the specific RBP that binds.

In the mature RNA molecule, exons are spliced together between the 5' and 3' untranslated regions. A 5' cap is attached to the 5' untranslated region, and a poly-A tail is attached to the 3' untranslated region. RNA-binding proteins associate with the 5' and 3' untranslated regions.

The protein-coding region of mRNA is flanked by 5′ and 3′ untranslated regions (UTRs). The presence of RNA-binding proteins at the 5′ or 3′ UTR influences the stability of the RNA molecule.

RNA Stability and microRNAs

In addition to RBPs that bind to and control (increase or decrease) RNA stability, other elements called microRNAs can bind to the RNA molecule. These microRNAs, or miRNAs, are short RNA molecules that are only 21–24 nucleotides in length. The miRNAs are made in the nucleus as longer pre-miRNAs. These pre-miRNAs are chopped into mature miRNAs by a protein called dicer. Like transcription factors and RBPs, mature miRNAs recognize a specific sequence and bind to the RNA; however, miRNAs also associate with a ribonucleoprotein complex called the RNA-induced silencing complex (RISC). RISC binds along with the miRNA to degrade the target mRNA. Together, miRNAs and the RISC complex rapidly destroy the RNA molecule.

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