Arx1 Is a Nuclear Export Receptor for the 60S Ribosomal Subunit in Yeast

Abstract

We previously showed that nuclear export of the large (60S) ribosomal subunit relies on Nmd3 in a Crm1-dependent manner. Recently the general mRNA export factor, the Mtr2/Mex67 heterodimer, was shown to act as an export receptor in parallel with Crm1. These observations raise the possibility that nuclear export of the 60S subunit in Saccharomyces cerevisiae requires multiple export receptors. Here, we show that the previously characterized 60S subunit biogenesis factor, Arx1, also acts as an export receptor for the 60S subunit. We found that deletion of ARX1 was synthetic lethal with nmd3 and mtr2 mutants and was synthetic sick with several nucleoporin mutants. Deletion of ARX1 led to accumulation of pre-60S particles in the nucleus that were enriched for Nmd3, Crm1, Mex67, and Mtr2, suggesting that in the absence of Arx1, 60S export is impaired even though the subunit is loaded with export receptors. Finally, Arx1 interacted with several nucleoporins in yeast two-hybrid as well as in vitro assays. These results show that Arx1 can directly bridge the interaction between the pre-60S particle and the NPC and thus is a third export receptor for the 60S subunit in yeast.

Ribosome Biogenesis in the YeastSaccharomyces cerevisiae

“…At least five proteins (Arx1, Bud20, Ecm1, Mex67, and Nmd3) function together to enable nuclear export of pre-60S subunits Gadal et al 2001b;Bradatsch et al 2007;Yao et al 2007Yao et al , 2010Hung et al 2008;Bassler et al 2012).…”

Specific RNP capture with antisense LNA/DNA mixmers

“…Its ortholog in yeast, Arx1, was identified to be a nuclear export receptor for the 60S ribosomal subunit (Hung et al 2008). Structural data in yeast show that Arx1 interacts with the 28S rRNA expansion segment ES27L (Greber et al 2012).…”

Bcp1 Is the Nuclear Chaperone of Rpl23 in Saccharomyces cerevisiae

“…Consequently, the ribosomal proteins must be imported into the nucleus for assembly with the rRNAs. After ribosome assemblies have achieved a certain stage of maturation, export factors are loaded to direct these huge complexes to cross the nuclear membrane through the nuclear pore complexes (1)(2)(3)(4)(5)(6). In the cytoplasm, ribosomes undergo additional steps in the maturation process; the trans-acting factors that are exported with nascent ribosomal subunits need to be stripped off, additional ribosomal proteins are added, and in the case of the 40S subunit, the final rRNA processing occurs (7,8).…”

“…BCP1 is an essential gene involved in the export of Mss4 (11), a phosphatidylinositol (PI) 2 4-phosphate 5-kinase that catalyzes the phosphorylation of PI4-phosphate and acts with the PI4-kinase, Stt4p, at the plasma membrane to generate PI4,5P 2 (12,13). Phosphoinositols are critical small signaling molecules that regulate cellular functions.…”