Three proteins of the U7-specific Sm ring function as the molecular ruler to determine the site of 3'-end processing in mammalian histone pre-mRNA

Mol Cell Biol. 2009 Aug;29(15):4045-56. doi: 10.1128/MCB.00296-09. Epub 2009 May 26.


Cleavage of histone pre-mRNAs at the 3' end is guided by the U7 snRNP, which is a component of a larger 3'-end processing complex. To identify other components of this complex, we isolated proteins that stably associate with a fragment of histone pre-mRNA containing all necessary processing elements and a biotin affinity tag at the 5' end. Among the isolated proteins, we identified three well-characterized processing factors: the stem-loop binding protein (SLBP), which interacts with the stem-loop structure upstream of the cleavage site, and both Lsm11 and SmB, which are components of the U7-specific Sm ring. We also identified 3'hExo/Eri-1, a multifunctional 3' exonuclease that is known to trim the 3' end of 5.8S rRNA. 3'hExo primarily binds to the downstream portion of the stem-loop structure in mature histone mRNA, with the upstream portion being occupied by SLBP. The two proteins bind their respective RNA sites in a cooperative manner, and 3'hExo can recruit SLBP to a mutant stem-loop that itself does not interact with SLBP. UV-cross-linking studies used to characterize interactions within the processing complex demonstrated that 3'hExo also interacts in a U7-dependent manner with unprocessed histone pre-mRNA. However, this interaction is not required for the cleavage reaction. The region between the cleavage site and the U7-binding site interacts with three low-molecular-weight proteins, which were identified as components of the U7-specific Sm core: SmB, SmD3, and Lsm10. These proteins likely rigidify the substrate and function as the molecular ruler in determining the site of cleavage.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Base Sequence
  • Binding Sites / genetics
  • Blotting, Western
  • Cell Line, Tumor
  • Histones / genetics*
  • Immunoprecipitation
  • Mice
  • Nucleic Acid Conformation
  • Protein Binding
  • RNA Precursors / genetics
  • RNA Precursors / metabolism*
  • RNA Processing, Post-Transcriptional*
  • RNA, Spliced Leader / genetics
  • RNA, Spliced Leader / metabolism
  • Ribonucleoprotein, U7 Small Nuclear / chemistry
  • Ribonucleoprotein, U7 Small Nuclear / genetics
  • Ribonucleoprotein, U7 Small Nuclear / metabolism*


  • 3' Untranslated Regions
  • Histones
  • RNA Precursors
  • RNA, Spliced Leader
  • Ribonucleoprotein, U7 Small Nuclear