Genomic context tunes sequence-encoded RNA processing

Genomic position dominated RNA production levels and differentially tuned RNA processing at tens of thousands of ectopic loci, with portable introns retaining native-like splicing.

• Why it matters: Sequence-encoded RNA processing and genomic context are hard to disentangle at native loci, limiting how well processing “modules” can be understood and transferred.
• What they did: RNA-processing elements were integrated into endogenous transcription units at tens of thousands of mapped positions, with different elements placed at shared positions to uncouple sequence from position.
• The result: A cryptic polyadenylation site used natively only upon U1 inhibition was rarely used ectopically, while native-locus introns partially retained splicing across thousands of positions; SON depletion reduced splicing of two introns, preferentially near speckles, and chromatin state, GC content, and speckle proximity tuned splicing in opposite directions.

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