Naslov
The rules and impact of nonsense-mediated mRNA decay in human cancers

Autori
Lindeboom, Rik ; Supek, Fran ; Lehner, Ben

Izvornik
Nature genetics (1061-4036) 48 (2016), 10; 1112-1118

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Cancer ; Gene expression ; Gene regulation ; Genomics

Sažetak
Premature termination codons (PTCs) cause a large proportion of inherited human genetic diseases. PTC-containing transcripts can be degraded by an mRNA surveillance pathway termed nonsense-mediated mRNA decay (NMD). However, the efficiency of NMD varies ; it is inefficient when a PTC is located downstream of the last exon junction complex (EJC). We used matched exome and transcriptome data from 9, 769 human tumors to systematically elucidate the rules of NMD targeting in human cells. An integrated model incorporating multiple rules beyond the canonical EJC model explains approximately three-fourths of the non-random variance in NMD efficiency across thousands of PTCs. We also show that dosage compensation may sometimes mask the effects of NMD. Applying the NMD model identifies signatures of both positive and negative selection on NMD-triggering mutations in human tumors and provides a classification for tumor-suppressor genes.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Računarstvo, Biotehnologija

POVEZANOST RADA