Alternative splicing of murine T-cell receptor beta-chain transcripts

Abstract

Variable processing of heteronuclear RNA into multiple, defined species of messenger RNA is a well-established phenomenon in a number of systems, including myelin basic protein, calcitonin, troponin T4 and immunoglobulins. Within a single B cell, immunoglobulin heavy-chain peptides often exist as two related but distinct species, a membrane-bound form and a secreted form, both of which originate from the same germline constant(C)-region gene via alternative RNA processing pathways. Furthermore, at certain stages of B-cell development, a single variable(V)-region element can be concurrently expressed in immunoglobulins of both the IgM and IgD isotypes, presumably resulting from the alternative splicing of one variable-region exon to different constant-region genes. We report here the existence of an alternative RNA splicing pathway available to murine T-cell receptor (TCR) beta-chain transcripts. Sequence analysis of beta-chain complementary DNA clones reveals a C beta 1 species containing a 72-base pair (bp) insertion between the joining (J beta) and C beta elements. This sequence is inserted via an alternative splicing pathway available to C beta 1 transcripts. The optional exon is located between the J beta 1 cluster and the first exon of C beta 1. Interestingly, this element can be spliced to C beta 2 in the New Zealand White mouse, in which the C beta 1 gene is deleted. Use of the alternative splicing pathway varies between 1% and 18% of total C beta clones, depending on the source of isolation.