Alternative splicing of EKLF/KLF1 in murine primary erythroid tissues

Exp Hematol. 2015 Jan;43(1):65-70. doi: 10.1016/j.exphem.2014.08.007. Epub 2014 Oct 2.

Abstract

Alternative splicing has emerged as a vital way to expand the functional repertoire of a set number of mammalian genes. For example, such changes can dramatically alter the function and cellular localization of transcription factors. With this in mind, we addressed whether EKLF/KLF1 mRNA, coding for a transcription factor that plays a critical role in erythropoietic gene regulation, is alternatively spliced. We find that EKLF mRNA undergoes exon skipping only in primary tissues and that this splice variant (SV) remains at a very low level in both embryonic and adult erythroid cells, as well as during terminal differentiation. The resultant protein is truncated and partially encodes a non-erythroid Krüppel-like factor amino acid sequence. Its overexpression can alter full-length erythroid Krüppel-like factor function at selected promoters. We discuss these results in the context of stress and with respect to recent global studies on the role of alternative splicing during terminal erythroid differentiation.

Publication types

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

MeSH terms

  • Alternative Splicing*
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Lineage
  • Erythroid Cells / metabolism*
  • Erythropoiesis / genetics*
  • Female
  • Gene Expression Regulation
  • Genes, Reporter
  • Humans
  • K562 Cells
  • Kruppel-Like Transcription Factors / genetics*
  • Kruppel-Like Transcription Factors / physiology
  • Leukemia, Erythroblastic, Acute / pathology
  • Mice
  • Molecular Sequence Data
  • Phlebotomy
  • Promoter Regions, Genetic
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology
  • Protein Structure, Tertiary
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Recombinant Fusion Proteins / metabolism
  • Spleen / metabolism
  • Transcription, Genetic
  • Transcriptional Activation

Substances

  • Kruppel-Like Transcription Factors
  • Protein Isoforms
  • RNA, Messenger
  • RNA, Neoplasm
  • Recombinant Fusion Proteins
  • erythroid Kruppel-like factor