Widespread specific intron-retention events in nuclear RNA complexes identified by sedimentation analysis of pluripotent cellular extracts
Abstract
Many essential cellular processes require RNA to interact with protein(s) to form ribonucleic protein complexes (RNPs). For example, all cellular proteins are produced by the ribosome - a large and stable RNP, gene splicing requires a choreography of numerous small and large RNPs, even the replication of telomeric DNA requires an RNP. All these examples are stable RNPs that exhibit specific sedimentation rates (e.g., in a sucrose gradient) based on the composition of RNA and protein. In this study we aimed to identify RNA components of discrete RNPs on a transcriptome-wide scale. Using sucrose-gradient sedimentation followed by sequencing, we identified 1,057 RNA transcripts, both coding and noncoding, that are likely to be components of cellular RNPs. We named these transcripts Gradient Enriched Transcripts (GETs). GETs were predominantly nuclear, metabolically stable, and they were not the major splice isoforms but instead each contained a specific retained intron. Collectively our study reveals a widespread phenomenon of a specific intron being retained in a stable nuclear RNPs.
- Received January 17, 2025.
- Accepted August 21, 2025.
- Published by Cold Spring Harbor Laboratory Press
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