Translational control of SCL-isoform expression in hematopoietic lineage choice.
We investigated the translational regulation of SCL protein expression and its role in hematopoietic lineage choice. We show that the expression of different SCL protein isoforms is regulated by signal transduction pathways that modulate translation initiation factor (eIF) function. A conserved small upstream open reading frame (uORF) in SCL transcripts acts as a cis-regulatory element for isoform expression. At the onset of erythroid differentiation, truncated SCL protein isoforms arise by alternative translation initiation and favor the erythroid lineage. In comparison, full-length SCL proteins are more efficient at enhancing the megakaryocyte lineage. Together, our studies unravel translational control as a novel mechanism regulating hematopoietic outcome.
Calkhoven
Cornelis F
CF
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Muller
Christine
C
Martin
Richard
R
Krosl
Goradz
G
Pietsch
Hubertus
H
Hoang
Trang
T
Leutz
Achim
A
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015152:Blotting, Northern; D015153:Blotting, Western; D001853:Bone Marrow / Q000382:microbiology / Q000473:pathology*; D019556:COS Cells; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics*; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D005434:Flow Cytometry; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D006413:Hematopoietic System / Q000502:physiology*; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology; D016366:Open Reading Frames; D010448:Peptide Initiation Factors / Q000378:metabolism; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D015852:Eukaryotic Initiation Factor-2; D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C067143:TAL1 protein, human