Details

Autor(en) / Beteiligte

• Milcarek, Christine
• Martincic, Kathleen
• Alkan, Serkan A
• Cheatle, Alys
• Borghesi, Lisa

Titel

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

Ist Teil von

• Nature immunology, 2009-10, Vol.10 (10), p.1102-1109

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2009

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.