Abstract
Ribogenesis is a multistep error-prone process that is actively monitored by quality control mechanisms. How ribosomal RNA synthesis, pre-rRNA processing and nucleolar surveillance are integrated is unclear. Nor is it understood how defective ribosomes are recognized. We report in budding yeast that, in vivo, the interaction between the transcription elongation factor Spt5 and Rpa190, the largest subunit of RNA polymerase (Pol) I, requires the Spt5 C-terminal region (CTR), a conserved and highly repetitive domain that is reminiscent of the RNA Pol II C-terminal domain (CTD). We show that this sequence is also required for the interaction between Spt5 and Nrd1, an RNA specific binding protein, and an exosome cofactor. Both the Spt4-Spt5, and the Nrd1-Nab3 complexes interact functionally with Rrp6, and colocalize at the rDNA. Mutations in the RNA binding domain of Nrd1, but not in its RNA Pol II CTD-interacting domain, and mutations in the RRM of Nab3 led to the accumulation of normal and aberrant polyadenylated pre-rRNAs. Altogether these results indicate that Nrd1-Nab3 contributes to recruiting the nucleolar surveillance to elongating polymerases to survey nascent rRNA transcripts.
Highlights
Ribosome synthesis is a complex pathway that involves hundreds of individual error-prone reactions
We have focused on the 39-59 pathway, which involves the addition of short poly(A) tails at the 39-ends of unfaithful rRNA transcripts by TRAMP complexes, followed by complete digestion by the exosome
Interactomics revealed an extensive network of physical interactions between Spt5 and numerous pre-ribosome constituents (Fig 6A), consistent with a function of the Spt4–Spt5 complex in ribosome synthesis
Summary
Ribosome synthesis is a complex pathway that involves hundreds of individual error-prone reactions (reviewed in [1]). Nucleolar surveillance is evolutionarily conserved and involves both 59-39 ([3,4]) and 39-59 RNA decay pathways ([5,6,7]). The biomedical relevance of rapidly clearing the cells of damaged, and potentially harmful, ribosomes is exemplified by the observation that chemicallyaltered ribosomes accumulate in the neurons of patients suffering from Alzeihmer’s disease (reviewed in [2]). A major crop pollinator, suffering from colony collapse disorder (CCD) accumulate polyadenylated rRNAs ([8]), a hallmark of ribosome degradation, which highlights the importance to understand ribosome surveillance mechanisms
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