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Rapid mRNA degradation via AU-rich elements is a critical mechanism for preventing the overproduction of potent cytokines such as tumor necrosis factor (TNF) and granulocyte-macrophage colony stimulating factor (GM-CSF). [37] AU-rich elements also regulate the biosynthesis of proto-oncogenic transcription factors like c-Jun and c-Fos. [38]
AREs are one of the most common determinants of RNA stability in mammalian cells. [1] The function of AREs was originally discovered by Shaw and Kamen in 1986. [2] AREs are defined as a region with frequent adenine and uridine bases in a mRNA. They usually target the mRNA for rapid degradation.
Non-stop decay (NSD) is a cellular mechanism of mRNA surveillance to detect mRNA molecules lacking a stop codon and prevent these mRNAs from translation. The non-stop decay pathway releases ribosomes that have reached the far 3' end of an mRNA and guides the mRNA to the exosome complex, or to RNase R in bacteria for selective degradation.
Sequences within the 3′-UTR also have the ability to degrade or stabilize the mRNA transcript. Modifications that control a transcript's stability allow expression of a gene to be rapidly controlled without altering translation rates. One group of elements in the 3′-UTR that can help destabilize an mRNA transcript are the AU-rich elements ...
The poly(A) tail is important for the nuclear export, translation and stability of mRNA. The tail is shortened over time, and, when it is short enough, the mRNA is enzymatically degraded. [2] However, in a few cell types, mRNAs with short poly(A) tails are stored for later activation by re-polyadenylation in the cytosol. [3]
Prokaryotic mRNA degradation poses a difficulty to researchers developing mRNA vaccines. This is the case because the degradation means that mRNA is not stable, and might not deliver the vaccine effectively; [ 8 ] this problem has been combated by chemically modifying mRNA, using several different kinds of chemicals, such as lipids , lipid-like ...
After being produced, the stability and distribution of the different transcripts is regulated (post-transcriptional regulation) by means of RNA binding protein (RBP) that control the various steps and rates controlling events such as alternative splicing, nuclear degradation (), processing, nuclear export (three alternative pathways), sequestration in P-bodies for storage or degradation and ...
Both are initiated through degradation of the mRNA's poly(A) tail, resulting in removal of the mRNA's 5' cap. 5'-to-3' degradation of the transcript occurs by XRN1 exonuclease in cytoplasmic bodies called P-bodies. [19] 3'-to-5' degradation of the transcript is conducted by the exosome and Ski complex. [18]
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