KRC TRANSCRIPTS - IDENTIFICATION OF AN UNUSUAL ALTERNATIVE SPLICING EVENT

Mouse KRC is a large zinc finger protein that binds to the kappa B mot if of gene transcription and to the recognition signal sequences for t he somatic recombination of the immunoglobulin and T-cell receptor gen e segments. The mouse KRC gene is more than 70 kilobases (kb) in size, and contains at least seven exons. with the largest transcript being similar to 9.5 kb. Multiple differentially spliced transcripts of KRC were identified in thymus and brain, which would result in the product ion of multiple KRC protein isoforms with different N-termini and numb er of DNA binding domains. Alternative splicing events leading to the production of these multiple transcripts have been elucidated. Of part icular interest are the exclusions in some transcripts of sequences fr om a gigantic exon of 5487 base pairs (bp), or from an exon of 176 bp. Both potentially deleted exons code for zinc finger motifs that are e ssential components of the N-terminal and C-terminal DNA binding domai ns, respectively. Another intriguing phenomenon found in some KRC tran scripts is the skipping of a 459 bp fragment within the gigantic exon that would code for the N-terminal DNA binding domain. Bacterial fusio n proteins derived from this fragment bind specifically to KRC target DNAs. Apparently, distinct alternative splicing events could eliminate the N-terminal DNA binding domain of KRC.