An alternative UPF1 isoform drives conditional remodeling of nonsense-mediated mRNA decay

ABSTRACT: The nonsense-mediated mRNA decay (NMD) pathway monitors translation termination in order to degrade transcripts with premature stop codons and regulate thousands of human genes. Here we show that an alternative mammalian-specific isoform of the core NMD factor UPF1, termed UPF1LL, enables condition-dependent remodeling of NMD specificity. Previous studies indicate that the extension of a conserved regulatory loop in the UPF1LL helicase core confers a decreased propensity to dissociate from RNA upon ATP hydrolysis relative to UPF1SL, the major UPF1 isoform. Using biochemical and transcriptome-wide approaches, we find that UPF1LL can circumvent the protective RNA binding proteins PTBP1 and hnRNP L to preferentially bind and down-regulate transcripts with long 3'UTRs normally shielded from NM

SUBMITTER: Sarah, E Fritz 

PROVIDER: S-SCDT-EMBOJ-2021-108898 | biostudies-other |

REPOSITORIES: biostudies-other