| dc.description.abstracteng | During all steps of nuclear RNA maturation, aberrant RNAs can be generated. However, nuclear quality control mechanisms ensure that immature or aberrant RNAs are retained in the nucleus and subsequently degraded to prevent faulty transcripts from being exported into the cytoplasm and participate in cellular processes. In this study, the multifunctional RNA-binding protein Npl3 was identified to be a general key surveillance factor for mRNAs and rRNAs. Here we show, that the protein binds to pre-mRNAs after the 5’-capping is completed. A properly processed 5’-cap is bound by the cap binding complex (CBC). This is detected by Npl3 and correctly capped pre-mRNAs are further processed. However, if the 5’-cap was not properly added, Npl3 prevents the export of these faulty transcripts by recruiting the 5’ to 3’ degradation machinery Rat1-Rai1 via interaction with Rai1. Interestingly, the quality control of Npl3 does not seem to be restricted to the 5’-end of an mRNA, because we could also show that Npl3 is required to recruit the 3’ to 5’ degradation machinery. In this case, Npl3 loads the TRAMP complex component Air2 to the 3’-end of mRNAs, inducing the subsequent TRAMP complex formation and therefore the degradation by the nuclear exosome.
Strikingly, Npl3 functions also in ribosome biogenesis. Here, we show that Npl3 is loaded co-transcriptionally to the 5’-end of emerging pre-rRNAs and it is important for early rRNA processing and surveillance. Npl3 interacts with the SSU processome and is important for its assembly. Furthermore, Npl3 is required to load the 3’ to 5’ degradation machinery to pre-rRNAs. This is important for the rRNA degradation during regular processing and for degradation of aberrant precursors especially the 23S rRNA.
Remarkably, the functions of Npl3 in mRNA and rRNA biogenesis are quite similar, as Npl3 in both cases is required for RNA processing and surveillance to ensure that only high-quality RNAs can exit the nucleus and engage in protein synthesis. Npl3 prevents the nuclear export of aberrant transcripts and recruits the 5’ to 3’ and the 3’to 5’ degradation machineries. Their recruitment requires co-factors as the TRAMP complex or Rai1, which Npl3 loads to the RNA, before it is released, and the RNA is degraded. Thus, our work has uncovered Npl3 as a general guard protein for mRNA and rRNA processing that determines whether an RNA is further processed or eliminated from the cell. | de |