AI Article Synopsis
- The nonsense-mediated decay (NMD) pathway helps get rid of faulty mRNAs that tell the cell to stop making proteins too early and also helps control normal mRNAs that make full-length proteins.
- In humans, NMD works by cutting and breaking down these faulty mRNAs, involving some complicated processes and a specific group of enzymes.
- The study found that a protein called DIS3L2 is important for this process in human cells, and it works together with other proteins to help get rid of the unwanted mRNAs.
Article Abstract
The nonsense-mediated decay (NMD) pathway selectively degrades mRNAs carrying a premature translation-termination codon but also regulates the abundance of a large number of physiological mRNAs that encode full-length proteins. In human cells, NMD-targeted mRNAs are degraded by endonucleolytic cleavage and exonucleolytic degradation from both 5-' and 3'-ends. This is done by a process not yet completely understood that recruits decapping and 5'-to-3' exonuclease activities, as well as deadenylating and 3'-to-5' exonuclease exosome activities. In yeast, DIS3/Rrp44 protein is the catalytic subunit of the exosome, but in humans, there are three known paralogues of this enzyme: DIS3, DIS3L1, and DIS3L2. However, little is known about their role in NMD. Here, we show that some NMD-targets are DIS3L2 substrates in human cells. In addition, we observed that DIS3L2 acts over full-length transcripts, through a process that also involves UPF1. Moreover, DIS3L2-mediated decay is dependent on the activity of the terminal uridylyl transferases Zcchc6/11 (TUT7/4). Together, our findings establish a role for DIS3L2 and uridylation in NMD.
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| http://dx.doi.org/10.1016/j.bbrc.2019.08.105 | DOI Listing |
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