Sa. Wuensch et al., Murine B cell differentiation is accompanied by programmed expression of multiple novel beta-galactoside alpha 2,6-sialyltransferase mRNA forms, GLYCOBIOLOG, 10(1), 2000, pp. 67-75
ST6Gal I (beta-galactoside alpha 2,6-sialyltransferase, ST6N) elaborates th
e ubiquitously expressed alpha 2,6-sialyl linkage, A number of ST6Gal I mRN
A isoforms, differing only in their 5'-UT regions, is transcribed from a si
ngle mouse gene, Siat1. In B-lineage cells, alpha 2,6-sialic acid serves as
extracellular ligand for CD22, a participant in cell activation via an int
racellular signaling network of tyrosine kinases and SHP phosphastase, Acti
vation and terminal differentiation of mature B cells into plasma cells is
accompanied by the appearance of at least four distinct ST6Gal I mRNA isofo
rms, Resting splenic B-lymphocytes isolated from 8-12 wk C56B1/6 mice expre
ssed almost exclusively the Exons Q+O-containing form, which is the likely
homolog to the previously documented human Y+Z and rat -1+0 forms, lit vitr
o activation using recombinant CD40-ligand and conditioned media from T-hel
per cells resulted in a 2- to 3-fold elevation of overall ST6Gal I mRNA abu
ndance by Day 3, This coincided with repression of the Q+O form, and appear
ance of three new isoforms containing 5'-untranslated sequences X-1, X-2, o
r X-3. The X-1 form persisted through Day 10, when the transition of B cell
s to plasma cells was completed as evidence by disappearance of CD22 mRNA,
In contrast, the X-2 form only transiently appeared at Day 3 and declined t
o barely detectable levels by Day 7, Expression of the X-3 form, a minor mR
NA form, paralleled the X-2 form. The divergent 5'-UT exons are dispersed o
ver 69 kb of linear genomic space of Siat1, Mutually exclusive utilization
of these 5'-UT exons in transcripts predicts separate and distinct promoter
regulatory regions for each mRNA isoform.