Transcription elongation factor ELL2 directs immunoglobulin secretion in plasma cells by stimulating altered RNA processing

摘要

Immunoglobulin secretion is modulated by a competition between use of a weak promoter proximal poly(A) site and a non-consensus splice site in the last secretory-specific exon of the heavy chain pre-mRNA. RNA polymerase II transcription elongation factor ELL2, induced in plasma cells, enhanced both polyadenylation and exon skipping with the Igh gene and reporter constructs. Lowering ELL2 expression by hnRNP F transfection or siRNA reduced secretory-specific forms of IgH mRNA. ELL2 and polyadenylation factor CstF-64 co-tracked with RNA polymerase II across the Igh mu and gamma gene segments; association of both factors was blocked by ELL2 siRNA. Thus loading of ELL2 and CstF-64 on RNAP-II was linked, causative for enhanced proximal poly(A) site use and necessary for IgH mRNA processing.