Global splicing pattern reversion during somatic cell reprogramming

Cell Rep. 2013 Oct 31;5(2):357-66. doi: 10.1016/j.celrep.2013.09.016. Epub 2013 Oct 17.

Abstract

Alternative splicing generates multiple transcripts from a single gene, and cell-type-specific splicing profiles are important for the properties and functions of the cells. Recently, somatic cells have been shown to undergo dedifferentiation after the forced expression of transcription factors. However, it remains unclear whether somatic cell splicing is reorganized during reprogramming. Here, by combining deep sequencing with high-throughput absolute qRT-PCR, we show that somatic splicing profiles revert to pluripotent ones during reprogramming. Remarkably, the splicing pattern in pluripotent stem cells resembles that in testes, and the regulatory regions have specific characteristics in length and sequence. Furthermore, our siRNA screen has identified RNA-binding proteins that regulate splicing events in iPSCs. We have then demonstrated that two of the RNA-binding proteins, U2af1 and Srsf3, play a role in somatic cell reprogramming. Our results indicate that the drastic alteration in splicing represents part of the molecular network involved in the reprogramming process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cellular Reprogramming*
  • Exons
  • Gene Expression Regulation
  • Induced Pluripotent Stem Cells / metabolism*
  • Mice
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • RNA Interference
  • RNA Splicing*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism
  • Serine-Arginine Splicing Factors
  • Splicing Factor U2AF

Substances

  • Nuclear Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • Splicing Factor U2AF
  • Srsf3 protein, mouse
  • Zrsr1 protein, mouse
  • Serine-Arginine Splicing Factors

Associated data

  • GEO/GSE45916
  • GEO/GSE46149