Nuclear matrix factor hnRNP U/SAF-A exerts a global control of alternative splicing by regulating U2 snRNP maturation

Mol Cell. 2012 Mar 9;45(5):656-68. doi: 10.1016/j.molcel.2012.01.009. Epub 2012 Feb 9.


The nuclear matrix-associated hnRNP U/SAF-A protein has been implicated in diverse pathways from transcriptional regulation to telomere length control to X inactivation, but the precise mechanism underlying each of these processes has remained elusive. Here, we report hnRNP U as a regulator of SMN2 splicing from a custom RNAi screen. Genome-wide analysis by CLIP-seq reveals that hnRNP U binds virtually to all classes of regulatory noncoding RNAs, including all snRNAs required for splicing of both major and minor classes of introns, leading to the discovery that hnRNP U regulates U2 snRNP maturation and Cajal body morphology in the nucleus. Global analysis of hnRNP U-dependent splicing by RNA-seq coupled with bioinformatic analysis of associated splicing signals suggests a general rule for splice site selection through modulating the core splicing machinery. These findings exemplify hnRNP U/SAF-A as a potent regulator of nuclear ribonucleoprotein particles in diverse gene expression pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Coiled Bodies / metabolism
  • HeLa Cells
  • Heterogeneous-Nuclear Ribonucleoprotein U / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein U / metabolism
  • Heterogeneous-Nuclear Ribonucleoprotein U / physiology*
  • Humans
  • Mass Spectrometry
  • Ribonucleoprotein, U2 Small Nuclear / metabolism*
  • Survival of Motor Neuron 2 Protein / genetics


  • Heterogeneous-Nuclear Ribonucleoprotein U
  • Ribonucleoprotein, U2 Small Nuclear
  • SMN2 protein, human
  • Survival of Motor Neuron 2 Protein

Associated data

  • GEO/GSE34491