Total RNA sequencing reveals nascent transcription and widespread co-transcriptional splicing in the human brain
Abstract
Transcriptome sequencing allows for analysis of mature RNAs at base pair resolution. Here we show that RNA-seq can also be used for studying nascent RNAs undergoing transcription. We sequenced total RNA from human brain and liver and found a large fraction of reads (up to 40%) within introns. Intronic RNAs were abundant in brain tissue, particularly for genes involved in axonal growth and synaptic transmission. Moreover, we detected significant differences in intronic RNA levels between fetal and adult brains. We show that the pattern of intronic sequence read coverage is explained by nascent transcription in combination with co-transcriptional splicing. Further analysis of co-transcriptional splicing indicates a correlation between slowly removed introns and alternative splicing. Our data show that sequencing of total RNA provides unique insight into the transcriptional processes in the cell, with particular importance for normal brain development.
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Intronic reads form a decreasing gradient from the 5′ to the 3′ end of the intron, which depends on the kinetics of RNA Pol II and co-transcriptional splicing and leads to a saw-tooth pattern of read coverage over the gene.
“Indeed, intronic reads form a decreasing gradient from the 5′ to the 3′ end of the intron. This gradient depends on the kinetics of RNA Pol II and co‐transcriptional splicing and leads to formation of a “saw‐tooth” pattern of read coverage over the length of the gene (Ameur et al, 2011).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Ameur et al, 2011
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References 51 · Cited by 323
- Authors
- Ameur, A., Zaghlool, A., Halvardson, J., Wetterbom, A., Gyllensten, U., Cavelier, L., & Feuk, L.
- Affiliations
- Uppsala University (SE)
- Science for Life Laboratory (SE)
- Corresponding author
- Cavelier, Lucia
- Feuk, Lars
- Venue
- Nature Structural & Molecular Biology
- Published
- 2011-11-06
- Volume
- 18
- Issue
- 12
- Pages
- 1435-1440
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W1974272975
- Cited by
- 323
- References
- 51
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 18 · 2023: 16 · 2022: 22 · 2021: 42 · 2020: 22 · 2019: 20 · 2018: 17 · 2017: 27 · 2016: 24 · 2015: 30 · 2014: 28 · 2013: 17 · 2012: 20
- FWCI
- 8.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- co-transcriptional splicing, nascent RNA, alternative splicing, human brain, fetal brain development, axon growth, synaptic transmission, liver, transcriptome sequencing, intron retention
- MeSH terms
- Animals, Brain, Pan troglodytes, Humans, Introns, Liver, RNA, RNA Splicing, Transcription, Genetic, Sequence Analysis, RNA, Gene Expression Profiling, Transcriptome
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