Journal
NUCLEIC ACIDS RESEARCH
Volume 45, Issue 16, Pages 9716-9725Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkx617
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Funding
- Associazione Italiana Ricerca sul Cancro (AIRC) [15217]
- AIRC TRansforming IDEas in Oncological research (TRIDEO) [17182]
- HuGeF
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Defining the in vivo folding pathway of cellular RNAs is essential to understand how they reach their final native conformation. We here introduce a novel method, named Structural Probing of Elongating Transcripts (SPET-seq), that permits single-base resolution analysis of transcription intermediates' secondary structures on a transcriptome-wide scale, enabling base-resolution analysis of the RNA folding events. Our results suggest that cotranscriptional RNA folding in vivo is a mixture of cooperative folding events, in which local RNA secondary structure elements are formed as they get transcribed, and non-cooperative events, in which 5 '-halves of long-range helices get sequestered into transient non-native interactions until their 3 ' counterparts have been transcribed. Together our work provides the first transcriptome-scale overview of RNA cotranscriptional folding in a living organism.
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