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Erythroid-specific processing of human beta spectrin I pre-mRNA
ZL Chu, A Wickrema, SB Krantz and JC Winkelmann
Department of Internal Medicine, University of Cincinnati College of
Medicine, OH 45267-0508.
Erythroid cells express a unique form of beta spectrin I as a result of
tissue-specific alternative pre-mRNA processing. Nonerythroid cells that
express the beta spectrin I gene include four additional exons at the 3'
end of the mature transcript, leading to elongation of the carboxyl
terminus of the protein. The nonerythroid beta spectrin I isoform is not
present in the red blood cell membrane skeleton; the erythroid isoform is
not detected in other cell types. Therefore, developing erythroid cells
acquire this tissue-specific pre-mRNA processing activity during
differentiation. In the present study, we investigated the developmental
timing of erythroid-specific pre-mRNA processing in human erythroid
precursors. Partially purified human peripheral blood burst forming
uniterythroid (BFU-E) cells were grown in culture for 5 to 12 days. beta
Spectrin I mRNA transcripts were analyzed at different time points by S1
nuclease mapping. The processing of beta spectrin I transcripts was found
to be exclusively erythroid from day 5 onward, indicating that
erythroid-specific processing is not linked temporally to assembly of the
mature erythroid membrane skeleton. Human erythroleukemia (HEL) cells had
both erythroid and nonerythroid transcripts, indicating that both
processing patterns can coexist. Induction of erythroid differentiation in
HEL cells using hemin resulted in a partial switch toward the erythroid
processing pattern of beta spectrin I transcripts. Using a genomic S1 probe
that spans the erythroid polyadenylation signal, we found that a
substantial portion of the transcripts detected by the erythroid cDNA S1
probe (in both cultured BFU-E and HEL cells) is incompletely processed
pre-mRNA precursors. Poly(A) RNA selection before S1 analysis showed that
the unprocessed transcripts are not polyadenylated. We conclude that (1)
erythroid-specific pre-mRNA processing activity is present early in
erythroid differentiation; (2) beta spectrin I transcripts that are
unprocessed at the 3' end accumulate, awaiting either erythroid or
nonerythroid processing pathways, from which observation we infer that the
regulated alternative pathways are both inefficient; and (3) HEL cells
offer a human cell culture model in which to study the balance between the
two pre-mRNA processing pathways. We speculate that erythroid cells evolved
this tissue-specific pre-mRNA processing machinery for other erythroid
genes in addition to beta spectrin I.
Volume 84,
Issue 6,
pp. 1992-1999,
09/15/1994
Copyright © 1994 by The American Society of Hematology
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