Coexpression of μ and γ1 heavy chains can occur by a discontinuous transcription mechanism from the same unrearranged chromosome

Maureen Nolan-Willard, Michael T. Berton, Philip Tucker

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

We previously documented that a single BCL1 leukemia cell can produce μ and γ1 immunoglobulin heavy chains with identical variable segments in an allelically excluded fashion without heavy chain constant region gene rearrangement. To understand the mechanism of dual μ/γ1 synthesis in BCL1 subclones, we have analyzed mature and pre-RNA at the nascent and steady-state levels. We find μ and γ1 sequences linked in pre-RNA. However, the primary μ and γ1transcription units are about the same length (≈15 kilobases). Initiation of γ1 pre-RNA occurs upstream of Cγ1 at sites identical to those seen in lipopolysaccharide/interieukin-4-induced normal B cells. We propose that dual μ/γ1 RNA synthesis occurs by a discontinuous transcription mechanism involving either trans-splicing or ligation of μ pre-RNA initiated 5′ of the variable-diversity-joining region to γ1 pre-RNA initiated 5′ of Cγ1.

Original languageEnglish (US)
Pages (from-to)1234-1238
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number4
DOIs
StatePublished - Feb 15 1992

Keywords

  • Class switching
  • Immunoglobulin gene regulation
  • RNA processing

ASJC Scopus subject areas

  • General

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