Processing of endogenous pre-mRNAs in association with SC-35 domains is gene specific

Analysis of six endogenous pre-mRNAs demonstrates that localization at the periphery or within splicing factor-rich (SC-35) domains is not restricted to a few unusually abundant pre-mRNAs, but is apparently a more common para digm of many protein-coding genes. Different genes are preferentially trans cribed and their RNAs processed in different compartments relative to SC-35 domains. These differences do not simply correlate with the complexity, nu clear abundance, or position within overall nuclear space. The distribution of spliceosome assembly factor SC-35 did not simply mirror the distributio n of individual pre-mRNAs, but rather suggested that individual domains con tain both specific pre-mRNA(s) as well as excess splicing factors. This is consistent with a multifunctional compartment, to which some gene loci and their RNAs have access and others do not. Despite similar molar abundance i n muscle fiber nuclei, nascent transcript "trees" of highly complex dystrop hin RNA are cotranscriptionally spliced outside of SC-35 domains, whereas p osttranscriptional "tracks" of more mature myosin heavy chain transcripts o verlap domains. Further analyses supported that endogenous pre-mRNAs exhibi t distinct structural organization that may reflect not only the expression and complexity of the gene, but also constraints of its chromosomal contex t and kinetics of its RNA metabolism.