Transcription elongation factor ELL2 directs immunoglobulin secretion in plasma cells by stimulating altered RNA processing.
Immunoglobulin secretion is modulated by competition between the use of a weak promoter-proximal poly(A) site and a nonconsensus splice site in the final secretory-specific exon of the heavy chain pre-mRNA. The RNA polymerase II transcription elongation factor ELL2, which is induced in plasma cells, enhanced both polyadenylation and exon skipping with the gene encoding the immunoglobulin heavy-chain complex (Igh) and reporter constructs. Lowering ELL2 expression by transfection of heterogenous ribonucleoprotein F (hnRNP F) or small interfering RNA resulted in lower abundance of secretory-specific forms of immunoglobulin heavy-chain mRNA. ELL2 and the polyadenylation factor CstF-64 tracked together with RNA polymerase II across the Igh mu- and gamma-gene segments; the association of both factors was blocked by ELL2-specific small interfering RNA. Thus, loading of ELL2 and CstF-64 on RNA polymerase II was linked, caused enhanced use of the proximal poly(A) site and was necessary for processing of immunoglobulin heavy-chain mRNA.
Martincic
Kathleen
K
University of Pittsburgh, School of Medicine, Department of Immunology, Pittsburgh, Pennsylvania, USA.
Alkan
Serkan A
SA
Cheatle
Alys
A
Borghesi
Lisa
L
Milcarek
Christine
C
D000818:Animals; D039241:Cleavage Stimulation Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism*; D012322:RNA Precursors / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D039241:Cleavage Stimulation Factor; C492658:Cstf2t protein, mouse; D007143:Immunoglobulin Heavy Chains; D012322:RNA Precursors; D035602:Transcriptional Elongation Factors