A regulatory role for CRM1 in multi-directional trafficking of splicing snRNPs in the mammalian nucleus

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28 Citations (Scopus)

Abstract

Distinct pathways of ribonucleoprotein transport exist within the nucleus, connected to their biogenesis and maturation. These occur despite evidence that the major mechanism for their movement within the nucleus is passive diffusion. Using fusions of Sm proteins to YFP, CFP and photoactivatable GFP, I have demonstrated that pathways with uni-directional bulk flow of complexes can be maintained within the nucleus despite multi-directional exchange of individual complexes. Newly imported splicing small nuclear ribonucleoproteins (snRNPs) exchange between Cajal bodies (CBs) within a nucleus and access the cytoplasm, but are unable to accumulate in speckles. By contrast, snRNPs at steady-state exchange freely in any direction between CBs and speckles, but cannot leave the nucleus. In addition to these surprising qualitative observations in the behaviour of nuclear complexes, sensitive live-cell microscopy techniques can detect subtle quantitative disturbances in nuclear dynamics before they have had an effect on overall nuclear organization. Inhibition of the nuclear export factor, CRM1, using leptomycin B results in a change in the dynamics of interaction of newly imported snRNPs with CBs. Together with the detection of interactions of CRM1 with Sm proteins and the survival of motor neurons (SMN) protein, these studies suggest that the export receptor CRM1 is a key player in the molecular mechanism for maintaining these pathways. Its role in snRNP trafficking, however, appears to be distinct from its previously identified role in small nucleolar RNP (snoRNP) maturation.

Original languageEnglish
Pages (from-to)1540-1550
Number of pages11
JournalJournal of Cell Science
Volume120
Issue number9
DOIs
Publication statusPublished - 1 May 2007

Keywords

  • Cajal body
  • snRNPs
  • nucleus
  • CRM1
  • SPINAL MUSCULAR-ATROPHY
  • SMALL NUCLEOLAR RNAS
  • IN-VIVO
  • MESSENGER-RNA
  • CAJAL BODIES
  • U-SNRNPS
  • SPLICEOSOMAL SNRNPS
  • CAP TRIMETHYLATION
  • ASSEMBLY PATHWAY
  • COILED BODIES

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