Aaaaaaaaa

AUUUArepeat-

oh t

Poly (A) ribonuclease

Poly (A) ribonuclease

FIGURE 12.28 ARE Sequence Facilitates Digestion of Eukaryotic mRNA

A) The structure of undegraded eukaryotic mRNA shows the AUUUA repeat sequence, the cap and the poly (A) tail. B) ARE-binding protein recognizes a repeated AUUUA sequence. C) Poly (A) ribonuclease degrades the poly (A) tail. D) Endonucleases sever the mRNA at multiple sites.

Endonucleases

Endonucleases

Nonsense-mediated decay of mRNA is triggered by the presence of premature stop codons.

d. Errors during RNA editing (presumably, although not directly demonstrated).

Nonsense-mediated decay is triggered whenever there is a stop codon more than 50-55 nucleotides upstream of the final exon-exon junction created during splicing. This requires that the location of the exon-exon splice junctions should somehow be marked on the mature mRNA. In animal cells exon-exon junctions are labeled when the primary transcript is converted to the mature mRNA during the splicing process. A complex of proteins, known as the exon junction complex (EJC) is bound to the mRNA about 20-24 nucleotides upstream of each exon-exon junction (Fig. 12.29).

Two of the three Upf proteins then bind to the exon junction complex and some of the original members of the EJC are lost. Upf3 binds first, while the mRNA is still inside the nucleus. Upf2 binds after the mRNA has exited the nucleus. During the first round of translation, the ribosome displaces the EJCs as it moves along the mRNA. If there is a premature stop codon, the ribosome finishes translating before all of the EJC complexes have been bumped off the mRNA. In this case, the termination complex, which includes the release factor plus Upf1, interacts with the remaining EJC (Fig. 12.29). This apparently involves the binding of Upf1 by the other two Upf proteins. This in turn triggers destruction of the mRNA molecule.

FIGURE 12.29 NonsenseMediated Decay of Eukaryotic mRNA

The primary transcript is capped and tailed and the introns are spliced out to give mature mRNA. In this case the mRNA contains a premature termination codon. During splicing the mRNA is loaded with exon junction complexes (EJC) upstream of each exon-exon junction. Upf3 protein binds to the EJC. The mRNA leaves the nucleus and Upf2 protein binds to the EJC. The ribosome loads onto the mRNA and the first round of translation occurs. If translation does not remove all of the EJCs, then nonsense-mediated decay is triggered by binding of release factor (RF) plus Upfl to the remaining EJC. Numbered circles represent Upfl, Upf2 and Upf3.

Primary Transcript

Premature stop codon i

Capping, tailing and splicing

Mature mRNA

AAAAAAAAA t

Loading of exon junction

COMPLEX (ejc) AND Upf3

Was this article helpful?

0 0

Post a comment