The C-terminal extension of Lsm4 interacts directly with the 3' end of the histone mRNP and is required for efficient histone mRNA degradation

RNA. 2014 Jan;20(1):88-102. doi: 10.1261/rna.042531.113. Epub 2013 Nov 19.


Metazoan replication-dependent histone mRNAs are the only known eukaryotic mRNAs that lack a poly(A) tail, ending instead in a conserved stem-loop sequence, which is bound to the stem-loop binding protein (SLBP) on the histone mRNP. Histone mRNAs are rapidly degraded when DNA synthesis is inhibited in S phase in mammalian cells. Rapid degradation of histone mRNAs is initiated by oligouridylation of the 3' end of histone mRNAs and requires the cytoplasmic Lsm1-7 complex, which can bind to the oligo(U) tail. An exonuclease, 3'hExo, forms a ternary complex with SLBP and the stem-loop and is required for the initiation of histone mRNA degradation. The Lsm1-7 complex is also involved in degradation of polyadenylated mRNAs. It binds to the oligo(A) tail remaining after deadenylation, inhibiting translation and recruiting the enzymes required for decapping. Whether the Lsm1-7 complex interacts directly with other components of the mRNP is not known. We report here that the C-terminal extension of Lsm4 interacts directly with the histone mRNP, contacting both SLBP and 3'hExo. Mutants in the C-terminal tail of Lsm4 that prevent SLBP and 3'hExo binding reduce the rate of histone mRNA degradation when DNA synthesis is inhibited.

Keywords: ERI1; Lsm proteins; SLBP; histone mRNA; mRNA degradation.

Publication types

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

MeSH terms

  • 3' Flanking Region*
  • Amino Acid Sequence
  • Base Sequence
  • HeLa Cells
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Interaction Domains and Motifs / physiology
  • RNA Stability*
  • RNA, Messenger / metabolism
  • Ribonucleoproteins / metabolism*
  • Ribonucleoproteins, Small Nuclear / chemistry
  • Ribonucleoproteins, Small Nuclear / metabolism*
  • mRNA Cleavage and Polyadenylation Factors / chemistry
  • mRNA Cleavage and Polyadenylation Factors / metabolism*


  • Histones
  • LSM4 protein, human
  • Nuclear Proteins
  • RNA, Messenger
  • Ribonucleoproteins
  • Ribonucleoproteins, Small Nuclear
  • SLBP protein, human
  • mRNA Cleavage and Polyadenylation Factors
  • messenger ribonucleoprotein