Human PDCD2L Is an Export Substrate of CRM1 That Associates with 40S Ribosomal Subunit Precursors

Mol Cell Biol. 2016 Nov 28;36(24):3019-3032. doi: 10.1128/MCB.00303-16. Print 2016 Dec 15.

Abstract

Protein arginine methyltransferase 3 (PRMT3) forms a stable complex with 40S ribosomal protein S2 (RPS2) and contributes to ribosome biogenesis. However, the molecular mechanism by which PRMT3 influences ribosome biogenesis and/or function still remains unclear. Using quantitative proteomics, we identified human programmed cell death 2-like (PDCD2L) as a novel PRMT3-associated protein. Our data suggest that RPS2 promotes the formation of a conserved extraribosomal complex with PRMT3 and PDCD2L. We also show that PDCD2L associates with 40S subunit precursors that contain a 3'-extended form of the 18S rRNA (18S-E pre-rRNA) and several pre-40S maturation factors. PDCD2L shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner using a leucine-rich nuclear export signal that is sufficient to direct the export of a reporter protein. Although PDCD2L is not required for the biogenesis and export of 40S ribosomal subunits, we found that PDCD2L-null cells accumulate free 60S ribosomal subunits, which is indicative of a deficiency in 40S subunit availability. Our data also indicate that PDCD2L and its paralog, PDCD2, function redundantly in 40S ribosomal subunit production. Our findings uncover the existence of an extraribosomal complex consisting of PDCD2L, RPS2, and PRMT3 and support a role for PDCD2L in the late maturation of 40S ribosomal subunits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism*
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mass Spectrometry
  • Protein Binding
  • Protein-Arginine N-Methyltransferases / metabolism*
  • Proteomics / methods*
  • RNA-Binding Proteins / metabolism*
  • Ribosomal Proteins / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • PDCD2L protein, human
  • RNA-Binding Proteins
  • RPS2 protein, human
  • Ribosomal Proteins
  • PRMT3 protein, human
  • Protein-Arginine N-Methyltransferases