Krebber, H. | Search bioRxiv

bioRxiv2022

A potential function for the helicase Dbp5 in cytoplasmic quality control

Accurate translation requires correct mRNAs with intact open reading frames. Cells eliminate defective transcripts to prevent mistranslation by three cytoplasmic mRNA quality control events termed nonsense-mediated decay (NMD), no-go decay (NGD) and non-stop decay (NSD). Translation termination on correct transcripts requires Dbp5 (human DDX19), which delivers eRF1 to the ribosomes and prevents an early contact of eRF1 with eRF3, precluding the immediate dissociation of both release factors and subsequent termination readthrough. Here, we report evidence for an influence of Dbp5 on NMD, as it delivers eRF1 also to PTC-containing transcripts. In contrast to regular translation termination and NMD, functional NGD and NSD require the eRF1-eRF3-like proteins Dom34-Hbs1. We suggest that Dbp5 delivers Dom34 to NGD and NSD substrates as well. However, in contrast to regular termination, it does not prevent an Hbs1 contact, but allows formation of a ternary Dom34-Hbs1-Dbp5 complex. The Dbp5-mediated delivery of Dom34-Hbs1 in NGD and NSD might rather shield and position the complex to prevent a premature contact of Dom34 and Rli1 to prevent inefficient splitting of the ribosomal subunits. Together, we have gathered evidence suggesting an important role of Dbp5 in cytoplasmic mRNA quality control.

cell biology↗

bioRxiv2021

Unraveling the stepwise maturation of the yeast telomerase

Telomerases elongate the ends of chromosomes required for cell immortality through their reverse transcriptase activity. By using the model organism Saccharomyces cerevisiae we defined the order in which the holoenzyme matures. First, a longer precursor of the telomerase RNA, TLC1 is transcribed and exported into the cytoplasm, where it associates with the protecting Sm-ring, the Est- and the Pop-proteins. This partly matured telomerase is re-import into the nucleus via Mtr10 and a novel TLC1-import factor, the karyopherin Cse1. Remarkably, while mutations in all known transport factors result in short telomere ends, mutation in CSE1 bypasses this defect and become Type I like survivors. Interestingly, both import receptors contact the Sm-ring for nuclear import, which therefore resembles a quality control step in the maturation process of the telomerase. The re-imported immature TLC1 is finally trimmed into the ~1150 nucleotide long mature form. TMG-capping of TLC1 finalizes maturation, leading to mature telomerase.

cell biology↗