The mRNA export factor Npl3 mediates the nuclear export of large ribosomal subunits

Abstract

The nuclear export of large ribonucleoparticles is complex and requires specific transport factors. Messenger RNAs are exported through the RNA-binding protein Npl3 and the interacting export receptor Mex67. Export of large ribosomal subunits also requires Mex67; however, in this case, Mex67 binds directly to the 5S ribosomal RNA (rRNA) and does not require the Npl3 adaptor. Here, we have discovered a new function of Npl3 in mediating the export of pre-60S ribosomal subunit independently of Mex67. Npl3 interacts with the 25S rRNA, ribosomal and ribosomeassociated proteins, as well as with the nuclear pore complex. Mutations in NPL3 lead to export defects of the large subunit and genetic interactions with other pre-60S export factors.

The Npl3 hnRNP prevents R-loop-mediated transcription–replication conflicts and genome instability

“…7), and there is a high enrichment of Rrm3 in ribosomal protein genes, the most highly transcribed class of genes in yeast. This is consistent with a previous study showing that Npl3 is preferentially associated with ribosomal protein mRNAs and other highly transcribed transcripts (Kim Guisbert et al 2005) and the reported role of Npl3 mediating nuclear export of large ribosomal subunits (Hackmann et al 2011). Rrm3 is preferentially observed in a gradient manner that increases toward the 39 end of RNAPII genes, following a pattern similar to that previously shown for Rrm3 in THO mutants (GomezGonzalez et al 2011), which is partially suppressed by RNase H1 overexpression (Fig.…”

Npl3, a new link between RNA-binding proteins and the maintenance of genome integrity

“…They bind poly-A RNA, function as Mex67 adaptors, shuttle between the nucleus and the cytoplasm, and participate in pre-ribosomal subunits export. 8,20,[42][43][44] Whereas Nab2 associates with mRNAs encoding transcriptionrelated proteins, Npl3 preferentially binds to transcripts encoding ribosomal proteins and other highly transcribed mRNAs, 45 suggesting specific functions for Nab2 and Npl3 in alternative mRNP biogenesis pathways. Conversely, overexpression of NPL3 reduces the hyperrecombination phenotype of the THO mutant hpr1Δ, suggesting the existence of partially overlapping functions of Npl3 and THO.…”

Eukaryotic ribosome biogenesis at a glance

“…The general mRNA export receptor Mex67 (Faza et al, 2012; and the HEAT-repeat-containing protein Rrp12 (Oeffinger et al, 2004) have been suggested to facilitate the export of both subunits, and several other factors such as Arx1, Ecm1, Bud20 and Npl3 have been implicated in the export of the large pre-60S subunit Bradatsch et al, 2007;Hackmann et al, 2011;Yao et al, 2010). Although these additional factors are tightly linked to the export process, most are non-essential proteins and it is likely that they function to optimise the export of these gigantic molecules.…”