Transcriptional analysis supports the expression of human snRNA variants and reveals U2 snRNA homeostasis by an abundant U2 variant

Abstract

SUMMARYAlthough expansion of snRNA genes in the human genome and sequence variation in expressed transcripts were both identified long ago, no study has comprehensively analyzed which genes are transcriptionally active. Here, we use comprehensive bioinformatic analysis to differentiate between similar or identical genomic loci to determine that 49 snRNA genes are actively transcribed. This greatly expands on previous observation of sequence variation within snRNA transcripts. Further analysis of U2 snRNA variants reveals sequence variation maintains conserved secondary structures, yet sensitizes these U2 snRNAs to modulation of assembly factors. Homeostasis of total U2 snRNA level is maintained by altering the ratio of canonical and an abundant U2 snRNA variant. Both canonical and variant snRNA promoters respond to MYC and appear differentially sensitive to increased MYC levels. Thus, we identify transcribed snRNA variants and the sequence variation within, and propose mechanisms of transcriptional and post-transcriptional regulation of snRNA levels and pre-mRNA splicing.HIGHLIGHTSChIP-seq of active promoters identifies uncharacterized snRNA genesTranscribed repetitive snRNA genes are distinguished from falsely-mapped snRNA lociU2 snRNA variants are sensitive to modulations in snRNP assemblyWidely expressed U2 snRNA variants provide homeostasis for total U2 snRNP levels