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Modifications of RNA processing modulate the expression of hemoglobin genes
P Kollia1, E Fibach, S M Najjar
1Laboratory of Chemical Biology and Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Summary
Post-transcriptional regulation, including RNA processing, plays a role in hemoglobin gene switching. Unprocessed globin transcripts correlate with gene silencing in adult erythroid cells and K562 cells.
Area of Science:
- Molecular Biology
- Genetics
- Hematology
Background:
- Hemoglobin gene expression undergoes developmental switching, involving sequential gene activation and silencing.
- Post-transcriptional mechanisms are hypothesized to modulate globin gene expression alongside transcriptional changes.
Purpose of the Study:
- To investigate the role of post-transcriptional regulation in hemoglobin gene silencing.
- To analyze globin RNA transcripts in human adult erythroid cells (hAEC) and K562 erythroleukemic cells.
Main Methods:
- Quantitative PCR analysis of globin RNA transcripts.
- Analysis of globin mRNA processing and localization in nucleus and cytoplasm.
Main Results:
- In hAEC, beta-globin mRNA is processed, while epsilon-globin transcripts are largely unspliced.
- In K562 cells, beta-globin mRNA is low and unspliced, contrasting with highly expressed epsilon- and gamma-globin transcripts.
- Unexpressed globin genes show predominantly unspliced transcripts, regardless of cellular location.
Conclusions:
- Changes in globin RNA transcript processing, in addition to transcription rates, contribute to developmental regulation of hemoglobin.
- Post-transcriptional mechanisms are critical for silencing specific globin genes during erythroid development.