Connections between Alternative Transcription and Alternative Splicing in Mammals

The majority of mammalian genes produce multiple transcripts resulting from alternative splicing (AS) and/or alternative transcription initiation (ATI) and alternative transcription termination (ATT). Comparative analysis of the number of alternative nucleotides, isoforms, and introns per locus in genes with different types of alternative events suggests that ATI and ATT contribute to the diversity of human and mouse transcriptome even more than AS. There is a strong negative correlation between AS and ATI in 5′ untranslated regions (UTRs) and AS in coding sequences (CDSs) but an even stronger positive correlation between AS in CDSs and ATT in 3′ UTRs. These observations could reflect preferential regulation of distinct, large groups of genes by different mechanisms: 1) regulation at the level of transcription initiation and initiation of translation resulting from ATI and AS in 5′ UTRs and 2) posttranslational regulation by different protein isoforms. The tight linkage between AS in CDSs and ATT in 3′ UTRs suggests that variability of 3′ UTRs mediates differential translational regulation of alternative protein forms. Together, the results imply coordinate evolution of AS and alternative transcription, processes that occur concomitantly within gene expression factories.