Intron gigantism, where genes contain megabase-sized introns, is observed across species, yet little is known about its purpose or regulation. Here we identify a unique gene expression program utilized for the proper expression of genes with intron gigantism. We find that two Drosophila genes with intron gigantism, kl-3 and kl-5 , are transcribed in a spatiotemporal manner over the course of spermatocyte differentiation, which spans ~90 hours. The introns of these genes contain megabases of simple satellite DNA repeats that comprise over 99% of the gene loci, and these satellite-DNA containing introns are transcribed. We identify two RNA-binding proteins that specifically localize to kl-3 and kl-5 transcripts and are needed for the successful transcription or processing of these genes. We propose that genes with intron gigantism require a unique gene expression program, which may serve as a platform to regulate gene expression during cellular differentiation.

12Intron gigantism, where genes contain megabase-sized introns, is observed across 13 species, yet little is known about its purpose or regulation. Here we identify a unique gene 14 expression program utilized for the proper expression of genes with intron gigantism. We 15 find that two Drosophila genes with intron gigantism, kl-3 and kl-5, are transcribed in a 16 spatiotemporal manner over the course of spermatocyte differentiation, which spans ~90 17 hours. The introns of these genes contain megabases of simple satellite DNA repeats that 18 comprise over 99% of the gene loci, and these satellite-DNA containing introns are 19 transcribed. We identify two RNA-binding proteins that specifically localize to kl-3 and kl-5 20 transcripts and are needed for the successful transcription or processing of these genes. We 21 propose that genes with intron gigantism require a unique gene expression program, which 22 may serve as a platform to regulate gene expression during cellular differentiation. 23 24 25