Knockdown of SLBP results in nuclear retention of histone mRNA

Kelly D Sullivan1, Thomas E Mullen, William F Marzluff

  • 1Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

RNA (New York, N.Y.)
|January 22, 2009
PubMed

Insights

Reduced stem-loop binding protein (SLBP) impairs histone mRNA export from the nucleus. This finding reveals a new role for SLBP in regulating histone mRNA metabolism and cell growth.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Histone mRNAs are unique among eukaryotic mRNAs as they lack polyadenylation.
  • Their maturation involves a critical endonucleolytic cleavage mediated by stem-loop binding protein (SLBP).
  • SLBP is known to be essential for histone mRNA processing, cytoplasmic export, translation, and degradation regulation.

Purpose of the Study:

  • To investigate the role of SLBP in histone mRNA metabolism.
  • To analyze histone mRNA metabolism in cells with significantly reduced SLBP levels.
  • To understand the impact of SLBP depletion on cell growth and histone mRNA fate.

Main Methods:

  • RNA interference (RNAi) was used to knock down SLBP levels in U2OS cells.
  • Cell growth rates and cell cycle progression (S-phase accumulation) were monitored.
  • Histone mRNA levels, processing status, and subcellular localization were analyzed.

Main Results:

  • Knocking down SLBP led to reduced cell growth and S-phase accumulation.
  • Histone mRNA levels decreased only modestly (twofold) despite SLBP reduction.
  • Processed histone mRNA accumulated in the nucleus and was not rapidly degraded upon DNA replication inhibition.

Conclusions:

  • SLBP plays a crucial, previously unrecognized role in the nuclear export of histone mRNA.
  • Reduced SLBP impacts cell cycle progression and histone mRNA metabolism.
  • These findings highlight a novel function of SLBP beyond its known roles in processing and translation.

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