Conservation of a masked nuclear export activity of La proteins and its effects on tRNA maturation

Mol Cell Biol. 2007 May;27(9):3303-12. doi: 10.1128/MCB.00026-07. Epub 2007 Feb 16.

Abstract

La is an RNA-processing-associated phosphoprotein so highly conserved that the human La protein (hLa) can replace the tRNA-processing function of the fission yeast La protein (Sla1p) in vivo. La proteins contain multiple trafficking elements that support interactions with RNAs in different subcellular locations. Prior data indicate that deletion of a nuclear retention element (NRE) causes nuclear export of La and dysfunctional processing of associated pre-tRNAs that are spliced but 5' and 3' unprocessed, with an accompanying decrease in tRNA-mediated suppression, in fission yeast. To further pursue these observations, we first identified conserved residues in the NREs of hLa and Sla1p that when substituted mimic the NRE deletion phenotype. NRE-defective La proteins then deleted of other motifs indicated that RNA recognition motif 1 (RRM1) is required for nuclear export. Mutations of conserved RRM1 residues restored nuclear accumulation of NRE-defective La proteins. Some RRM1 mutations restored nuclear accumulation, prevented disordered pre-tRNA processing, and restored suppression, indicating that the tRNA-related activity of RRM1 and its nuclear export activity could be functionally separated. When mapped onto an hLa structure, the export-sensitive residues comprised surfaces distinct from the RNA-binding surface of RRM1. The data indicate that the NRE has been conserved to mask or functionally override an equally conserved nuclear export activity of RRM1. The data suggest that conserved elements mediate nuclear retention, nuclear export, and RNA-binding activities of the multifunctional La protein and that their interrelationship contributes to the ability of La to engage its different classes of RNA ligands in different cellular locations.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Sequence
  • Autoantigens / chemistry*
  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Binding Sites
  • Cell Nucleus / metabolism*
  • Conserved Sequence*
  • Gene Deletion
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation / genetics
  • Nuclear Export Signals / physiology
  • Nucleic Acid Conformation
  • Protein Structure, Tertiary
  • RNA Splice Sites
  • RNA, Transfer / chemistry
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism*
  • Response Elements
  • Ribonucleoproteins / chemistry*
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*
  • SS-B Antigen

Substances

  • Autoantigens
  • Nuclear Export Signals
  • RNA Splice Sites
  • Ribonucleoproteins
  • RNA, Transfer